Excitationcontraction coupling

In view of the functional similarity between the heart and the diaphragm, there should be some similarities in their cellular contraction mechanisms, particularly their excitation-contraction coupling processes. This hypothesis has been supported by recent experimental evidence. Although the central role of calcium in the excitation-contraction coupling of skeletal muscle is well established, the cellular mechanisms by which calcium is made available to the contractile proteins during excitation to elicit contraction of the muscle remain unclear. It is generally believed that the activation of the contractile elements is essentially independent of extracellular calcium; the cyclic nature of Ca2+ fluxes in skeletal muscle during excitation-contraction coupling are regarded as strictly intracellular. In cardiac muscle, however, the passage of calcium across the cell membrane is of major importance; without it, there would be insufficient calcium from the sarcoplasmic reticulum to initiate contraction.

These classical notions have been challenged by the observation that isolated diaphragmatic fibers obtained from rats behave similarly to single papillary muscle fibers from the same animal. Indeed, a striking similarity has been observed between the contractile responses of diaphragmatic and papillary muscle fibers to extracellular calcium deprivation; in both cases there was complete abolition of twitch. However, no twitch abolition was observed with single soleus or extensor digitorum longus fibers (slow and fast peripheral skeletal muscles) when they were exposed to a calcium-free medium for 3 h. These data have been confirmed in vivo in hypocalcemic dogs (Aybiei..e.L§i: 1985). In these animals, a marked depression in diaphragmatic contractility was noted with hypocalcemia, whereas the sartorius, a peripheral skeletal muscle with a similar histochemical profile, was not affected. Therefore it appears that the diaphragm is a unique skeletal muscle that resembles cardiac muscle.

These results provide new insight into the mechanisms of diaphragmatic contraction, emphasizing the peculiarities of the diaphragm with respect to the other striated skeletal muscles. They also have important pharmacological implications. Owing to the similarities between the reliance of diaphragmatic and cardiac muscle fibers on extracellular calcium, it is conceivable that drugs or agents that exert a direct inotropic positive or negative effect on the myocardium may have a similar action on the diaphragm.

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