Overview of muscle physiology

  Skeletal muscles are usually under voluntary control to create movements

 

  • Pulse-like electrical messages from the central nervous system are sent down motor nerves.
  • At the neuromuscular junction, electrical signals induce the release of Acetylcholine (ACh, a neurotransmitter) from the axon terminal.
  • ACh diffuses across the cleft and acts on postsynaptic muscle fibres.
  • The ultimate consequence is muscle contraction that drives the skeleton to generate and support body movement.

 

        See an illustration of neuromuscular junctions.

       A. a schematic presentation B. a histological section

 

  Electrical events of the sarcolemma (the plasma membrane of a muscle fibre) underlie the muscle contraction

 Muscle action potential

 Figure 1. a schematic presentation showing a muscle action potential

  • The resting membrane potential (RMP) of a muscle cell is maintained around -90mV.
  • Membrane potential (Vm) rapidly arises after Ach stimulation. The phenomenon is called cell depolarization or cell excitation.
  • Excited muscle fibres contract; Vm drops back to the resting level (repolarization) in absence of further stimuli.
  • This transient, regenerative up-and-down voltage shift (within 1-2ms) is called muscle action potential.

 

Ion channel activities are the main contributory factor of these backstage events

 

excitation-contraction coupling

 Figure 2. a schematic presentation showing ion channels expressed by a muscle cell

  • The sarcolemma has high Cl- conductance via the exclusive chloride channel CLC-1. Together with certain K+ channels (they open randomly), ClC-1 stabilises the RMP, and contributes to repolarization.
  • ACh binds to and opens nAChR. These cation selective channels shift Vm in the positive direction.
  • Once Vm exceeds a threshold voltage, Nav, Cav and Kv channels are activated spontaneously.    

Nav1.4 (the votage-dependent Na+ channel on  skeletal muscles) opens rapidly and elicits a quick depolarization. However, it also inactivates immediately.

Increased cytoplasmic Ca2+, an important signal molecule, activates the muscular contractile apparatus (sarcomere) protein complexes responsible for generating muscle contraction) followed by the ultimate muscle contraction.

Delayed rectifier K+ channels bring Vm towards the resting state.

 

physiology to pathophysiology 

Now we can see that ion channels are critical for the normal function of skeletal muscles. Defects in ion channels would lead to diseases, for example myotonia.