Myogenic muscles: contraction generated by trigger from within the muscle.
- Found in cardiac muscle.
Neurogenic muscles: stimulated to contract by neural activity.
- Skeletal muscles innervated by motor neurons.
Tropomyosin: Double stranded protein spanning ~7 actin monomers. Blocks myosin binding sites on actin.
Troponin: A 3-subunit complex.
- TnC: Calcium-binding sites
- TnI: binds actIn
- TnT: binds Tropomyosin
- Calcium binds to TnC
- TnI releases actin
- Troponin-tropomyosin complex moves away from myosin-binding sites
- Myosin is free to bind to the actin
Muscles actively shorten and passively lengthen. Troponin and tropomyosin key in allowing muscle relaxation along with opposing muscle contractions.
Motor cortex and other motor control centres send signals through descending tract of spinal cord. Motor neuron (efferent) axons leave ventral root.
- Cell Bodies in the ventral horn
- These neurons innervate neurogenic muscle fibers.
- Size of ventral horn reflects extent of motor innervation.
This is usually under conscious control. Motor neurons innervate the skeletal muscles.
- Longest neuron in body
- Induce contraction and relaxation patterns for diff movts (antagonistic muscles)
- Acetylcholine = Neurotransmitter at the neuromuscular junction: always excitatory
- Action potential results in ACh release. VG Ca2+ channels open and increase in internal [Ca2+] leading to vesicle docking
- Binds nicotinic ACh receptor (nAChR) on skeletal muscles. nAChRs are ligand gated ion channels. Ions (mostly Na+) depolarize muscle
- Induces muscle contraction
- AChE (acetylcholinesterase) breaks down ACh into choline and acetate, terminating the signal.
- Presynaptic cell takes up and recycles choline. Acetate diffuses out of the synapse.
- Motor end plate: Regions of the myofiber where axon terminals of motor neuron synapse.
- Sarcolemma: myocyte membrane. Resting potential is ~-70mV
- ACh binds to nAChR, ion channel opens
- Na+ enter myofiber
- Sarcolemma depolarized, VG Na+ channels open,
- depolarization propagates to T-tubules (sarcolemmal invaginations)
- VG Ca2+ channels open
- Na+ and Ca2+ channels close
- VG K+ channels open, repolarization occurs
Skeletal Muscles: depolarize and repolarize quickly (short refractory period).
- AP = 5% of contraction-relaxation cycle
- 2nd AP can induce 2nd contraction even if muscle hasn’t relaxed
- Tetanus: Perpetual muscle spasm
- Results in summation and can lead to tetanus
Cardiac muscles: long repolarization phase (long refractory period).
- VG Ca2+ channels stay open longer
- AP = 50% of contraction-relaxation cycle
- Arrythmia: when a 2nd contraction occurs while the muscle is contracting.
- No summation or tetanus, but addition of contractions can lead to arrythmia
T-tubule: transverse tubules. Extensions/invaginations of the sarcolemma allow APs to propagate deep into myofiber quickly.
- System is extensive in large or quick-contracting muscles (e.g. fast-twitch skeletal muscles)
Sarcoplasmic Reticulum: muscle endoplasmic reticulum. Extensive network has high Ca2+ stores ([Ca2+] in cytoplasm is low)
- Ca2+ released from SR -> contraction. Ca2+ pumped back in SR -> relaxation.
Terminal Cisternae of SR: Enlargements of SR near T-tubules. They increase capacity of Ca2+ storage and ensure rapid Ca2+ delivery.
- Extensive in fast-twitch skeletal muscles, less developed in slow-twitch muscles (e.g cardiac muscle).
On sarcolemma...
- DHPR: VG Ca2+ channel abundant in T-tubules
- Ca2+ ATPase: pump Ca2+ out into ECF
- Na+/ Ca2+ exchanger (NaCaX)
On sarcoplasmic reticulum:
- RyR: Ca2+ channel
- SERCA: Ca2+ ATPase, pump Ca2+ back into SR
Cardiac muscle: Ca2+ induced Ca2+ release
- At rest: [Ca2+]i low
- DHPR channels closed at resting membrane potential
- [Ca2+] high in ECF and SR
- Myogenic depolarization opens DHPR channels
- ECF Ca2+ required to activate RyR
- Ryanodine receptors (RyR) open in response to local increases in [Ca2+]
- Elevated [Ca2+] allows more Ca2+ to escape the SR. This also triggers actino-myosin ATPase
- After repolarization, ion pumps (SERCA, NaCaX and sarcolemma Ca2+ ATPase) return Ca2+ to resting locations.
Skeletal muscle: Depolarization-induced Ca2+ release
- At rest: DHPR physically interact with RyR; Activation of RyR happens even if no Ca2+ ions move through DHPR (from ECF)
- As sarcolemma is depolarized DHPR channels open
- Conformational change in DHPR channel opens RyR
- Both result in increases in [Ca2+]i
- Relaxation is the same as in cardiac EC coupling.
Cell Morphology:
- Cardiac: Single cardiomyocytes about 10-20um in diameter and 100um in length
- Skeletal: Multiple cells fuse together into large myofibers 10-100um in diameter and 1-100 mm in length
Excitation:
- Cardiac: Myogenic and involuntary
- Skeletal: Neurogenic and usually voluntary
Action Potential:
- Cardiac: Slow repolarization with long refractory period
- Skeletal: Fast repolarization with short refractory period
EC Coupling:
- Cardiac: Ca2+-induced Ca2+ release
- Skeletal: Depolarization-induced Ca2+ release
Sarcoplasmic Reticulum:
- Cardiac: Well-developed terminal cisternae in birds and mammals. Poorly developed SR in lower vertebrates
- Skeletal: Amount of terminal cisternae depends on fiber type
Different types of muscle rely on specific arrangements of sarcomeres to carry out different functions.
- Hypothetical situation for one sarcomere: generates 5 pN of force and can shorten 0.5um
- 1000 of these sarcomeres in series = 2500 um long; generates 5 pN of force but can shorten 500um
- 1000 of these sarcomeres in parallel = 2.5 um long; shortens only 0.5um but can generate 5000 pN of force
- Muscle arrangment optimized for different types of contraction: maximal force vs maximal shortening.
Activated muscle can:
- shorten: e.g. lifting rock up
- lengthen: e.g. walking down, sitting, lowering rock down
- remain the same length (isometric): e.g. back muscles maintain posture
- Isometric contraction: Tension changes to allow muscle to remain the same length; same length, changing tension
- Isotonic contraction: tension remains unchanged and the muscle's length changes (e.g. lifting object at constant speed); same tension, changing length
- A muscle must be stretched before tension can be applied to load
- Tension increases isometrically (stretching of viscoelastic system) to overcome force exerted by load; then, muscle shortens if tension > load
- Series elastic components: Tendons, Z-discs, Cross-bridges
- Parallel elastic components: Sarcolemma, Muscle connective tissue
Twitch: contraction resulting from a single AP Latent period: time between stimulation and contraction (relies on time of EC coupling and stretch of series elastic components)
- Potential tension produced is low; Ca2+ is quickly lost.
- Ca2+ pumped back into SR before cross-bridges can fully stretch out the elastic elements.
Temporal Summation: Amounts of force generated by single AP add up as the frequency of AP increases.
- Second AP arrives before contraction finishes
- Strength of force generated increases with AP rate
- Successive APs = RyR channels opened with sufficient frequency, so Ca2+ keeps the myosin-binding sites on actin exposed
Tetanus: maintained contraction with repeated stimulation
- To maximize force, we need to maintain an active state
- Cross-bridges can cycle repeatedly until the elastic elements are stretched tightly and the full contractile potential of the muscle fiber is realized.
- In tetanus, maximal contractile response, maximal force generated.
Twitch vs tetanic contraction?
- Maximum tetanic force generation ~3-5x strength of twitch force generation
- In twitch: Ca2+ sequestered before full tension generated, but in tetanus: active state is prolonged
- Whole muscle generally operates at a tetanic level: maintained active state, fatigue results if prolonged.
Motor unit: a motor neuron and the muscle fibers it innervates.
- Each myofiber controlled by one motor neuron (but 1 neuron innervate many myofibers)
- At muscle level: many different motor units
- ↑ Recruitment= ↑ # of active motor units
- Whole muscle tension ↑ as more motor units send APs