Excitation-response coupling, membranes

Four different localizations of fatigue can be identified (a) decreased central command (b) decreased activation of the muscle membrane and the T-tubular system (c) decreased Ca release from the SR and (d) decreased response to the Ca release by the contractile proteins. The first two are partly extra-muscular while c and d are intramuscular responses to the excitation of the muscle membrane and often defined as excitation-contraction coupling. 

Figure 6.6. Excitation contraction coupling in skeletal muscle (a, b) and heart muscle (c). In skeletal muscle, the anesthetics receptor (DHPR) and the ryanodine receptor (RyR) are in direct contact (a). The conformational change to the former that occurs in response to membrane depolarization is sufficient to induce Ca release from the SR a flow of Ca across the plasma membrane is not necessary (b). In heart muscle, however, this direct link does not exist, and Ca must therefore enter through the DHPR first (c).

The maintenance of physiologic calcium concentrations in the intracellular and extracellular spaces is vital for the preservation and function of cell membranes propagation of neuromuscular activity regulation of endocrine and exocrine secretory functions blood coagulation cascade platelet adhesion process bone metabolism muscle cell excitation/contraction coupling and mediation of the elec-trophysiologic slow-channel response in cardiac and smooth-muscle tissue. 

Compared with normal muscle, dystrophic muscle exhibits delayed relaxation suggesting a disturbance of the excitation-contraction coupling mechanism. This process involves the release of calcium from the sarcoplasmic reticulum when the membrane becomes depolarised in response to a nerve impulse and the calcium ions in contact with the myofibrils cause them to contract. The muscle reverts to a relaxed condition when the calcium ions are removed by sequestration within the sarcoplasmic reticulum, a process that depends upon the active transport of calcium mediated by Ca -activated ATPase in conjunction with a repolarisation of the membrane. 

Calcium channel blockers act to uncouple excitation-contraction coupling in myocardium and smooth muscle by inhibiting the influx of Ca2 +. Vasodilation [1, 16] and depression of atrial and ventricular activity [17, 18] occur as a direct result. The calcium channel blockers prevent contraction in response to depolarization of the cell membrane by electrical stimulation [ 17,19-21 ] or by agonists such as high potassium ion concentrations [22-33], noradrenaline [22-24,28,29,32,33], 5-hydroxytryptamine [21,24] or prostaglandin F2a [21,24]. 

---