Fast sodium influx provides an initial step to trigger contractions in cat ventricle.

We examined the possibility that Na+ current (INa) may play a role in excitation-contraction coupling in cat ventricular myocytes. A voltage step from -70 to -40 mV produced a fast INa, followed by a small transient inward current, a brief loss in voltage control to more positive potentials, and a transient contraction (reduction in cell length, delta L). We established that 10 microM nifedipine completely blocked Ca2+ current but did not prevent delta L; nifedipine reduced it by approximately 15%. This nifedipine-insensitive delta L was abolished by 1-10 microM ryanodine, 1-10 microM saxitoxin (STX), and 0.1-1.0 mM Cd2+. The size of delta L increased with more negative holding potential (VH; delta L-VH relation). Maximal delta L was achieved at a VH of approximately -70 mV. Anthopleura toxin A (APA, 3-10 nM), which selectively slows inactivation of INa, increased the size of the nifedipine-insensitive delta L at all VH, thus producing a +7-mV shift in the delta L-VH relation that was not affected by the state of the sarcoplasmic reticulum (SR). APA also produced an increase in maximal delta L, which was no longer observed once the SR was significantly loaded. These effects of APA were prevented by preexposure to STX. The state of the SR Ca2+ stores did not affect the presence of a nifedipine-insensitive delta L but determined its magnitude, suggesting that delta L was not associated with Ca2+ overload. In summary, cat and guinea pig ventricular myocytes are alike in that they both exhibit distinct INa-dependent contractions. Whether these contractions are due to a sudden increase in subsarcolemmal Na+ as a result of fast INa or the depolarization and thus reversal of the Na+/Ca2+ exchange remains undetermined.