[Ca super(2+)] sub(i)-dependent membrane currents in guinea-pig ventricular cells in the absence of Na/Ca exchange

Transient inward currents (I sub(ti)) during oscillations of intracellular [Ca super(2+)] ([Ca super(2+)] sub(i)) in ventricular myocytes have been ascribed to Na/Ca exchange. We have investigated whether other Ca super(2+)-dependent membrane currents contribute to I sub(ti) in single guinea-pig ventricular myocytes, by examining membrane currents during [Ca super(2+)] sub(i) oscillations and during caffeine-induced Ca super(2+) release from the sarcoplasmic reticulum in the absence of Na super(+). Membrane currents were recorded during whole-cell voltage clamp and [Ca super(2+)] sub(i) measured simultaneously with fura-2. In the absence of Na/Ca exchange, i.e., with Li super(+), Cs super(+) or N-methyl-D-glucamine (NMDG super(+)) substituted for Na super(+), the cell could be loaded with Ca super(2+) by repetitive depolarizations to +10 mV, resulting in spontaneous [Ca super(2+)] sub(i) oscillations. During these oscillations, no inward currents were seen, but instead spontaneous Ca super(2+) release was accompanied by a shift of the membrane current in the outward direction at potentials between -40 mV and +60 mV. This [Ca super(2+)] sub(i)-dependent outward current shift was not abolished when NMDG super(+) was substituted for internal monovalent cations, nor was it sensitive to substitution of external Cl super(-). It was however, sensitive to the blockade of I sub(Ca) by verapamil. These results suggest that the transient outward current shift observed during spontaneous Ca super(2+) release represents [Ca super(2+)] sub(i)-dependent transient inhibition of I sub(Ca). Similarly, during the [Ca super(2+)] sub(i) transients induced by brief caffeine (10 mM) applications, we could not detect membrane currents attributable to a Ca super(2+)-activated nonselective cation channel, or to a Ca super(2+)-activated Cl super(-) channel; however, transient Ca super(2+)-dependent inhibition of I sub(Ca) was again observed. We conclude that neither the Ca super(2+)-activated nonselective cation channel nor the Ca super(2+)-activated Cl super(-) channel contribute significantly to the membrane currents during spontaneous [Ca super(2+)] sub(i) oscillations in guinea-pig ventricular myocytes. However, in the voltage range between -40 mV and +60 mV Ca super(2+)-dependent transient inhibition of I sub(Ca) will contribute to the oscillations of the membrane current.