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 voltage step from -70 to -40 mV produced a fast I(Na), 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, ΔL). We established that 10 μM nifedipine completely blocked Ca²⁺ current but did not prevent ΔL; nifedipine reduced it by ~15%. This nifedipine-insensitive ΔL was abolished by 1-10 μM ryanodine, 1-10 μM saxitoxin (STX), and 0.1-1.0 mM Cd²⁺. The size of ΔL increased with more negative holding potential (V(H); ΔL-V(H) relation). Maximal ΔL was achieved at a V(H) of approximately -70 mV. Anthopleura toxin A (APA, 3-10 nM), which selectively slows inactivation of I(Na), increased the size of the nifedipine-insensitive ΔL at all V(H), thus producing a +7-mV shift in the ΔL-V(H) relation that was not affected by the state of the sarcoplasmic reticulum (SR). APA also produced an increase in maximal ΔL, 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 ΔL but determined its magnitude, suggesting that ΔL was not associated with Ca²⁺ overload. In summary, cat and guinea pig ventricular myocytes are alike in that they both exhibit distinct I(Na)- dependent contractions. 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.