Slow inward calcium currents have no obvious role in muscle excitation–contraction coupling

It has been proposed 1 that an influx of calcium ions into twitch muscle fibres during an action potential might initiate contraction. However, when external Ca 2+ is lowered to 10 −8 M with EGTA, the fibres can produce normal twitches for many minutes 2,3 . Nevertheless, a clear Ca 2+ influx during contraction has been demonstrated 4,5 , and it has been found that phasic skeletal muscle has an inward calcium current ( I Ca ) 6,7 which can give rise to calcium spikes 8 . In certain conditions, a reduction in external Ca 2+ with 80–90 mM EGTA results in reversible blockade of excitation–contraction (e–c) coupling 9 , leading some authors to suggest 7,9–11 that extracellular Ca 2+ moved into the myoplasm due to I Ca may be involved in the e–c coupling mechanism that triggers contraction. This proposition was further supported by the localization of I Ca in the T-system, which circumvented the problem of the delay due to calcium diffusion from the surface membrane. We have now investigated whether I Ca has a clear role in initiating or sustaining contractions in twitch muscle fibres. Our approach was to decrease or eliminate I Ca with the calcium-blocking agent diltiazem (Herbesser) and to see how the twitch, tetanic and potassium-contracture tensions were affected. We found that I Ca could be decreased or cancelled with the calcium-blocking agent, but that the same concentration of the drug potentiated the twitch, tetanus and contractures. We conclude, therefore, that I Ca has no role in e–c coupling. A preliminary report of these results has been presented elsewhere 12 .