FAST SODIUM INFLUX PROVIDES AN INITIAL STEP TO TRIGGER CONTRACTIONS IN CAT VENTRICLE

We examined the possibility that Na+ current (I-Na) may play a role in excitation-contraction coupling in cat ventricular myocytes. A voltag e step from -70 to -40 mV produced a fast I-Na, followed by a small tr ansient inward current, a briefless in voltage control to more positiv e potentials, and a transient contraction (reduction in cell length, D elta L). We established that 10 mu M nifedipine completely blocked Ca2 + current but did not prevent Delta L; nifedipine reduced it by simila r to 15%. This nifedipine-insensitive Delta L was abolished by 1-10 mu M ryanodine, 1-10 mu M saxitoxin (STX), and 0.1-1.0 mM Cd2+. The size of Delta L increased with more negative holding potential (V-H; Delta L-V-H relation). Maximal Delta L was achieved at a V-H of approximate ly -70 mV. Anthopleura toxin A (APA, 3-10 nM), which selectively slows inactivation of I-Na, increased the size of the nifedipine-insensitiv e Delta L at all V-H, thus producing a +7-mV shift in the Delta L-V-H relation that was not affected by the state of the sarcoplasmic reticu lum (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 associ ated with Ca2+ overload. In summary, cat and guinea pig ventricular my ocytes are alike in that they both exhibit distinct I-Na-dependent con tractions. Whether these contractions are due to a sudden increase in subsarcolemmal Na+ as a result of fast I-Na, or the depolarization and thus reversal of the Na+/Ca2+ exchange remains undetermined.