[Ca2+]i-dependent membrane currents in guinea-pig ventricular cells in the absence of Na/Ca exchange.
Transient inward currents (Iti) during oscillations of intracellular [Ca2+] ([Ca2+]i) in ventricular myocytes have been ascribed to Na/Ca exchange. We have investigated whether other Ca2+-dependent membrane currents contribute to Iti in single guinea-pig ventricular myocytes, by examining membrane currents during [Ca2+]i oscillations and during caffeine-induced Ca2+ release from the sarcoplasmic reticulum in the absence of Na+. Membrane currents were recorded during whole-cell voltage clamp and [Ca2+]i measured simultaneously with fura-2. In the absence of Na/Ca exchange, i.e., with Li+, Cs+ or N-methyl-D-glucamine (NMDG+) substituted for Na+, the cell could be loaded with Ca2+ by repetitive depolarizations to +10 mV, resulting in spontaneous [Ca2+]i oscillations. During these oscillations, no inward currents were seen, but instead spontaneous Ca2+ release was accompanied by a shift of the membrane current in the outward direction at potentials between -40 mV and +60 mV. This [Ca2+]i-dependent outward current shift was not abolished when NMDG+ was substituted for internal monovalent cations, nor was it sensitive to substitution of external Cl-. It was however, sensitive to the blockade of ICa by verapamil. These results suggest that the transient outward current shift observed during spontaneous Ca2+ release represents [Ca2+]i-dependent transient inhibition of ICa. Similarly, during the [Ca2+]i transients induced by brief caffeine (10 mM) applications, we could not detect membrane currents attributable to a Ca2+-activated nonselective cation channel, or to a Ca2+-activated Cl- channel; however, transient Ca2+-dependent inhibition of ICa was again observed. We conclude that neither the Ca2+-activated nonselective cation channel nor the Ca2+-activated Cl- channel contribute significantly to the membrane currents during spontaneous [Ca2+]i oscillations in guinea-pig ventricular myocytes. However, in the voltage range between -40 mV and +60 mV Ca2+-dependent transient inhibition of ICa will contribute to the oscillations of the membrane current.
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002412:Cations / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002352:Carrier Proteins; D002412:Cations; D018118:Chloride Channels; D019831:Sodium-Calcium Exchanger; D002110:Caffeine; D012964:Sodium; D014700:Verapamil; D002118:Calcium