Fast sodium influx provides an initial step to trigger contractions in cat ventricle
Vites, A.M.; Wasserstrom, J.A.
American Journal of Physiology 271(2 Pt 2): H674-H686
1996
ISSN/ISBN: 0002-9513 PMID: 8770111 Document Number: 455998
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, DELTA-L). We established that 10 mu-M nifedipine completely blocked Ca-2+ current but did not prevent DELTA-L; nifedipine reduced it by apprx 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 Cd-2+. 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 approximately -70 mV. Anthopleura toxin A (APA, 3-10 nM), which selectively slows inactivation of I-Na, increased the size of the nifedipine-insensitive 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 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 Ca-2+ stores did not affect the presence of a nifedipine-insensitive DELTA-L but determined its magnitude, suggesting that DELTA-L was not associated with Ca-2+ 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+/Ca-2+ exchange remains undetermined.