THE ROLE OF THE NA+-CA2+ EXCHANGER IN THE RATE-DEPENDENT INCREASE IN CONTRACTION IN GUINEA-PIG VENTRICULAR MYOCYTES

1. The intracellular sodium activity (a(Na)(i)) contraction and membrane current were recorded simultaneously involtage-clamped guinea-pig ventricular myocytes. 2. Increasing the frequency (from 0.5 to 3 Hz) of voltage clamp pulses to 0 mV from a holding potential of -80 mV led to an increase in both a(Na)(i) and contraction. The rate-dependent increase in contraction was reduced by 25 mu M tetrodotoxin (TTX) and abolished with a holding potential of -40 mV. There was no rate-dependent rise in a(NA)(i) with a holding potential of -40 mV. These results suggest an important role of a(Na)(i) and in particular Na+ influx via Na+ channels during rate-dependent changes in contraction. 3. After an increase in frequency from 0.5 to 3 Hz, membrane current at the end of voltage clamp pulses became progressively more outward and the tail current upon repolarization became progressively more inward compared with those recorded at 0.5 Hz. TTX reduced the magnitude of both the outward and inward rate-dependent shifts of current. 4. The addition of extracellular CsCl blocked the inward rectifier potassium current (I-K,I-1) and the delayed rectifier (I-K), but did not change the rate-dependent shift in current. 5. The difference between current-voltage relationships at 0.5 and 3 Hz showed that the rate-dependent outward shift of current at the end of voltage clamp pulses was small at potentials negative to -20 mV, was larger at more positive potentials and was reduced by TTX at most potentials. The TTX-sensitive component reversed at -47 mV. 6. These results are consistent with a net increase in outward Na+-Ca2+ exchange current during voltage clamp pulse in response to the rise of a(Na)(i). The increase in outward current (resulting from either enhanced Ca2+ influx or reduced Ca2+ efflux) will augment the Ca2+ load of the cell and contribute to the rate-dependent increase in contraction.