A Markov model of human Cav2.3 channels and their modulation by Zn2+ (Neumaier et al 2020)
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Model information:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>---------------------</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>This is the readme for the model associated with the paper:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span class=SpellE><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>Neumaier</span></span><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'> F, <span class=SpellE>Apldogan</span> S, <span class=SpellE>Hescheler</span> J and Schneider T (2020) Zn<sup>2+</sup>-induced changes in Ca<sub>v</sub>2.3 channel function: An electrophysiological and modeling study. <i style='mso-bidi-font-style: normal'>J. Gen. Physiol. </i>(<a href="https://doi.org/10.1085/jgp.202012585">https://doi.org/10.1085/jgp.202012585</a>) </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='mso-ansi-language:EN-US'> <o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>Model information:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>------------------</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>The state diagram for the Ca<sub>v</sub>2.3 channel model in the absence of trace metal ions, which was developed based on channel structure, previous modeling studies and the ability to fit the data, is shown below (see also Fig. 15 in the accompanying paper). Horizontal transitions are voltage-dependent and correspond to movement of the four non-identical voltage-sensors and pore opening or closing respectively. Activation of two voltage-sensors (1 and 2) is obligatory for channel opening, giving rise to a total of 4 open states. Vertical transitions are voltage-independent and correspond to entry into and return from fast and slow inactivated states. The rates for voltage-dependent transitions were expressed in terms of the transition-state theory, and the parameters optimized by fitting the model to macroscopic currents recorded with various electrophysiological protocols (see below). The effects of Zn<sup>2+</sup> were implemented by assuming that Zn<sup>2+</sup> binding to a first site (<span class=SpellE>K<sub>Zn</sub></span>=0.003 <span class=SpellE>mM</span>) leads to electrostatic modification and mechanical slowing of one of the voltage-sensors while Zn<sup>2+</sup>-binding to a second, intra-pore site (<span class=SpellE>K<sub>Zn</sub></span>=0.1 <span class=SpellE>mM</span>) blocks the channel and modifies the opening and closing transitions (for details see the accompanying paper).</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal;text-autospace:none'><span lang=EN-US style='mso-ansi-language:EN-US'> <o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal;text-autospace:none'><span style='mso-no-proof:yes'><img border=0 width=790 height=423 id="_x0000_i1026" src="readme-Dateien/image001.jpg" alt="Beschreibung: Beschreibung: Beschreibung: Beschreibung: Beschreibung: C:\Users\Felix\Dropbox\5. MANUSCRIPTS\Eigene\Zn Effects and Model Neu\Model (Site 1+2)\New folder\Final_Revised\Cav23\readme-Dateien\image001.jpg"></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal;text-autospace:none'><span lang=EN-US style='mso-ansi-language:EN-US'> <o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal;text-autospace:none'><span lang=EN-US style='mso-ansi-language:EN-US'> <o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>Experimental and modeling conditions:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>------------------------</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>As a basis for model development, whole-cell patch-clamp recordings were performed in HEK-293 cells stably transfected with human Ca<sub>v</sub>2.3+β<sub>3</sub> channel subunits. All recordings were performed at room temperature and with near-physiological extracellular solutions that contained 4 <span class=SpellE>mM</span> free Ca<sup>2+</sup> for ionic currents or 4 <span class=SpellE>mM</span> free Mg<sup>2+</sup> and 0.1 <span class=SpellE>mM</span> free La<sup>3+</sup> for gating currents. The complete data set used for fitting included gating currents recorded at 15 different test potentials, long (400 <span class=SpellE>ms</span>) and short (25 <span class=SpellE>ms</span>) IV-currents recorded at 10 and 15 different test potentials respectively, IIV-currents recorded at 13 different test potentials and PPI-currents recorded at 14 different test potentials (for details on the voltage protocols see the accompanying paper and the simulations below). Parameter optimization and simulations were performed with an <i style='mso-bidi-font-style:normal'>in <span class=SpellE>silico</span></i> one-compartmental model of a HEK293 cell with diameter and length 21.851 µm, which corresponds to a sphere with a surface area of 1500 µm<sup>2</sup>. Default temperature, specific membrane capacitance and cytoplasmic resistivity were 22°C, 1 µF/cm<sup>2</sup> and 60 Ω*cm respectively. <span style='mso-spacerun:yes'> </span></span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='mso-ansi-language:EN-US'> <o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>---------</span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>2. Files:</span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>---------</span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>The following files are required to run one of the simulations:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>'Cav23.mod', which contains the Markov-type kinetic model of Cav2.3 channels</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>'vclamp_pl.mod', which contains a voltage clamp model with five levels that has been adopted from a previous model by <span class=SpellE>Balbi</span> et al. (Accession: 230137) </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>'IV <span class=SpellE>static.hoc</span>', 'IV <span class=SpellE>dynamic.hoc</span>', '<span class=SpellE>IVlong</span> <span class=SpellE>static.hoc</span>', '<span class=SpellE>IVlong</span> <span class=SpellE>dynamic.hoc</span>', '<span class=SpellE>IIV.hoc</span>' or '<span class=SpellE>PPI.hoc</span>', which contain the code for the different simulations described in section 4 </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>------------------------------------------------------------------</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>3. Compiling the mechanism (.mod) files and starting a simulation:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>------------------------------------------------------------------</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>Under <span class=SpellE>linux</span>:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>------------</span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>Compile the mod files using the command '<span class=SpellE>nrnivmodl</span>'.</span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>Use one of the following commands to start the simulations:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span class=SpellE><span class=GramE><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>nrngui</span></span></span><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'> IV <span class=SpellE>static.hoc</span></span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span class=SpellE><span class=GramE><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>nrngui</span></span></span><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'> IV <span class=SpellE>dynamic.hoc</span></span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span class=SpellE><span class=GramE><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>nrngui</span></span></span><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'> <span class=SpellE>IVlong</span> <span class=SpellE>static.hoc</span></span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span class=SpellE><span class=GramE><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>nrngui</span></span></span><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'> <span class=SpellE>IVlong</span> <span class=SpellE>dynamic.hoc</span></span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span class=SpellE><span class=GramE><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>nrngui</span></span></span><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'> <span class=SpellE>IIV.hoc</span></span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span class=SpellE><span class=GramE><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>nrngui</span></span></span><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'> <span class=SpellE>PPI.hoc</span></span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>Under Windows:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>--------------</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>Run '<span class=SpellE>mknrndll</span>' to compile the mod files.</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>Double click on one of the hoc files to start the simulations.</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>Under MAC OS X:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>---------------</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>Drag the model folder onto the <span class=SpellE>mknrndll</span> icon to compile the mod files.</span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>Drag one of the hoc files onto the <span class=SpellE>nrngui</span> icon to start the simulations.</span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>More information on running NEURON models can be found at</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span style='font-family:"Courier New"'><a href="https://senselab.med.yale.edu/ModelDB/NEURON_DwnldGuide.htm"><span lang=EN-US style='color:windowtext;mso-ansi-language:EN-US;text-decoration: none;text-underline:none'>https://senselab.med.yale.edu/ModelDB/NEURON_DwnldGuide.htm</span></a></span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='mso-ansi-language:EN-US'> <o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>----------------------</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>4. Simulation control:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>----------------------</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>When one of the hoc files is started, several panels for simulation control will appear. The <i>Clamp Control </i>panel (middle) contains the start button for running simulations and several clamp parameters, which can be changed by the user to modify the default voltage protocol. The <span class=SpellE><i>CaR</i></span><i> Control </i>panel (bottom) provides control over the number of channels per cm<sup>2</sup>, the single channel permeability and the free Zn<sup>2+</sup> concentration (in <span class=SpellE>mM</span>). The simulation speed can be adjusted by reducing or increasing the value of <span class=SpellE><span class=GramE>dt</span></span> in the <i>Run Control </i>panel (top). </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span style='font-family:"Courier New";mso-no-proof: yes'><img border=0 width=757 height=627 id="_x0000_i1025" src="readme-Dateien/image002.jpg" alt="Beschreibung: Beschreibung: Beschreibung: Beschreibung: Beschreibung: C:\Users\Felix\Dropbox\5. MANUSCRIPTS\Eigene\Zn Effects and Model Neu\Model (Site 1+2)\New folder\Final_Revised\Cav23\readme-Dateien\image002.jpg"></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>IV <span class=SpellE>static.hoc</span>:</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>-------------- </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>With the default clamp parameters, a click on the start button generates a family of current traces (bottom window) evoked with the same voltage protocol (top window) as that used in Fig. 15C, 16A and 17A (left panel) of the paper. </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='mso-ansi-language:EN-US'> <o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>IV <span class=SpellE>dynamic.hoc</span>: </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>---------------</span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>With the default clamp parameters, a click on the start button runs a dynamic simulation with the same voltage protocol as above but a clamping increment of 1 mV and plots the peak current-voltage relationship. </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span class=SpellE><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>IVlong</span></span><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'> <span class=SpellE>static.hoc</span>:</span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>------------------ </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>With the default clamp parameters, a click on the start button generates a family of current traces (bottom window) evoked with the same voltage protocol (top window) as that used in Fig. 15F and 17A (right panel) of the paper. </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='mso-ansi-language:EN-US'> <o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span class=SpellE><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>IVlong</span></span><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'> <span class=SpellE>dynamic.hoc</span>:</span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>------------------- </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>With the default clamp parameters, a click on the start button runs a dynamic simulation with the same voltage protocol as above but a clamping increment of 1 mV and plots the peak current-voltage relationship. </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span class=SpellE><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>IIV.hoc</span></span><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>: </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>--------</span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>With the default clamp parameters, a click on the start button generates a family of current traces (bottom window) evoked with the same voltage protocol (top window) as that used in Fig. 15D, 16C and 17B of the paper. </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span class=SpellE><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>PPI.hoc</span></span><span lang=EN-US style='font-family:"Courier New";mso-ansi-language:EN-US'>: </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>--------</span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'>With the default clamp parameters, a click on the start button generates a family of current traces (bottom window) evoked with the same voltage protocol (top window) as that used in Fig. 15E and 16B of the paper and plots the normalized pre-pulse inactivation relationship. The simulation speed can be increased by deselecting the Display Button at the bottom of the Clamp Control panel, which switches off display of the current traces during the simulation. </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language: EN-US'><o:p></o:p></span></p> <p class=MsoNormal style='margin-bottom:0cm;margin-bottom:.0001pt;line-height: normal;text-autospace:none'><span lang=EN-US style='font-family:"Courier New"; mso-ansi-language:EN-US'> </span><span lang=EN-US style='mso-ansi-language:EN-US'><o:p></o:p></span></p> <p class=MsoNormal><span lang=EN-US style='mso-ansi-language:EN-US'> <o:p></o:p></span></p> </div> </body> </html>
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A Markov model of human Cav2.3 channels and their modulation by Zn2+ (Neumaier et al 2020)
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