Question

When electrically stimulating a skeletal muscle, why is there a minimum stimulus intensity that must be reached in order to observe any contraction in the muscle? Provide a molecular explanation.

Answer 1

ELECTRICAL EVENT IN THE SKELETAL MUSCLE CONTRACTION

The resting membrane potential in skeletal muscle cells is similar to that in neurons, i.e. −70 to −90 mV. Unlike nerve cells, where the resting membrane potential is predominantly a result of K+ permeability, skeletal muscle cell resting membrane potential receives a significant contribution from Cl− conductance.

ACTION POTENTIAL GENERATION

A skeletal muscle action potential is generated when the motor endplate potential is sufficient to raise the surrounding sarcolemmal potential above the threshold for activation of the voltage gated Na+ channels that are abundant throughout the sarcolemma. When these channels are activated, the membrane is rapidly depolarized towards the Nernst potential for Na+ .

Once an action potential has been generated, it spreads as a wave over the sarcolemma. Skeletal muscle sarcolemma is characterized by invaginations called transverse- or t-tubules that run perpendicular to the surface of the cell deep into its body. By passing down the t-tubular membrane, the action potential is carried to the structures responsible for transducing an electrical into a chemical signal that will trigger activation of the contractile elements.

the t-tubular dihydropyridine receptors show marked amino acid homology with L-type voltage gated Ca2+ channels of other tissues, they do not function as Ca2+ channels. Their role in skeletal muscle is that of voltage sensors. When the action potential arrives in the t-tubule, the change in membrane potential leads to a conformational change in the α-subunit of the dihydropyridine receptor. This subunit consists of four transmembrane domains each of six segments.The first and sixth segments of adjacent domains are linked by alternating extracellular and cytoplasmic loops of amino acids. The voltage-induced conformational change results in the projection of the cytoplasmic loop between the second and third transmembrane domains deeper into the cytoplasm. Here, charged amino acid residues of the cytoplasmic loop come into proximity with those of a protein projecting towards the cytoplasmic surface of the t-tubule from the adjacent terminal swelling of the sarcoplasmic reticulum.

The result of the interaction between the dihydropyridine and ryanodine receptors is the opening of the channel pore of the latter. Ca2+ floods out of the sarcoplasmic reticulum down its concentration gradient into the cytoplasm where it acts as the trigger for contraction.