Mechanism of the use dependence of Ca2+ current in guinea-pig myocytes.
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.
Fedida
D
D
University Laboratory of Physiology, Oxford.
Noble
D
D
Spindler
A J
AJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001464:Barium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004533:Egtazic Acid / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000502:physiology*; D009200:Myocardial Contraction
D015220:Calcium Channels; D001464:Barium; D004533:Egtazic Acid; D007545:Isoproterenol; D004837:Epinephrine