Effect of Diltia Zem on Calcium Cup Rents and Excitation-Contraction Coupling in Frog Twitch Muscle

Abstract

One of the steps in the chain of events that briners about the contraction in frog twitch muscle cells is the release of calcium from the terminal cisternae. In his 1952 review, Sandow (1) proposed that an influx of Ca ions into twitch muscle cells during an action potential might initiate the contraction. A net calcium influx observed with flux measurements during contraction by Bianchi and Schanes in 1959 (2) and by Curtis in 1966 (3) supported Sandow’s proposition. However, Armstrong, Bezanilla and Horowicz (4) showed in 1972 that when external calcium is lowered with EGT A to 10^-8 M, isolated frog muscle fibers can produce normal twitches for many minutes. In 1979 Lűttgau (5) obtained similar results with tetani. Nevertheless, Stanfield in 1977 (6) and Sanchez and Stefani in 1978 (7) found that Dhasic skeletal muscles have an inward calcium current (l_Ca) which could be the basis of calcium spikes previously described by Beaty and Stefani in 1976 (8). Under certain conditions Barrett and Barrett (9) found that a reduction of external calcium with 80–90 mM EGTA brings about a reversible blockade of contraction leading some of the above mentioned authors (7,9) to suggest that extracellular calcium moving into the cell due to I_Ca may be involved in excitation-contraction (e-c) coupling. This proposition was further supported by the localization of I_Ca in the T-system found by Nicola Siri, Sanchez and Stefani (10). This finding circumvented the problem of the delay due to calcium diffusion from the surface membrane into the center of the fiber. Since calcium entry may play a role in e-c coupling, the present experiments were designed to analyze some of the effects that diltiazem has on the I_Ca and that blocking the I_Ca with this drug has on initiating and sustaining contractions in frog twitch muscle fibers.