Mechanism of the use dependence of Ca2+ current in guinea‐pig myocytes.

Abstract

1. The mechanism of the use‐dependent reduction and facilitation of the calcium current (iCa) in single guinea‐pig myocytes described by Fedida, Noble & Spindler (1988) has been examined by varying [Ca2+]o, [Ca2+]i and iCa. 2. Moderate enhancement of [Ca2+]i and [Ca2+]i changes produced by increasing [Ca2+]o reduces iCa and enhances the use‐dependent reduction. 3. Intracellular calcium overload, produced by reducing [Na+]o, greatly reduces iCa and almost totally eliminates the use‐dependent variations. 4. Use‐dependent reduction of iCa is also smaller after substituting external Ba2+ ions for Ca2+ ions. 5. When [Ca2+]i is buffered by intracellular EGTA sufficient to eliminate other [Ca2+]i‐dependent processes, such as contraction and Na+‐Ca2+ exchange, some use‐dependent reduction of iCa remains, although the effect is smaller. Use‐dependent facilitation of iCa is more prominent in the presence of internal EGTA. 6. The facilitation of iCa is abolished by Ba2+ replacement of Ca2+ and by the beta‐adrenoceptor agonist isoprenaline. This suggests that the facilitation is mediated by Ca2+ entry itself rather than membrane voltage. Facilitation is evident as a delay of current relaxation, even in the presence of internal EGTA. © 1988 The Physiological Society