CA2-PIG VENTRICULAR MYOCYTES( PERMEATION THROUGH NA+ CHANNELS IN GUINEA)

This study was undertaken to test the hypothesis that, in the absence of extracellular Na+, Ca2+ can permeate tetrodotoxin (TTX)-sensitive N a+ channels in Cs+-loaded whale cell voltage-clamped guinea pig ventri cular myocytes (22-24 degrees C). With 10 mM extracellular Ca2+, 50-ms step depolarizations (-50 to +25 mV) from holding potentials of -100 or -80 mV elicited fast and slow types of inward current: 1) a small ( < 400 pA) dihydropyridine-insensitive inward current that exhibited si milar voltage dependence to that of Na+ channels, with an activation t hreshold and peak near -45 mV and -30 mV, respectively; and 2) a large r and slower L-type Ca2+ current that activated and peaked at more pos itive potentials. Extracellular replacement of Ca2+ by Mg2+ abolished both currents. The lack of sensitivity of the low-threshold Ca2+-curre nt amplitude to 50 or 200 mu M Ni2+ suggests that this current is not produced by T-type Ca2+ current. Ln contrast, TTX dose dependently inh ibited the low-threshold Ca2+ current, with a half-maximal inhibition concentration of 2.4 mu M. Veratridine (10-50 mu M), a plant alkaloid that alters the gating and permeability properties of Na+ current, ind uced an outward shift of time-dependent current during steps to -25 mV and typical slowly decaying inward tail currents after repolarization to -80 mV. Cell exposure to 10 and 50 mu M extracellular Nai inhibite d the inward current by 21.2 +/- 3.9% (n = 23) and 14.0 +/- 3.0% (n = 14), respectively, whereas 1 mu M Na+ (n = 14) was without effect. The application of 200 mu M Na+ produced a small enhancement of the curre nt (+6.2 +/- 4.1%; n = 14) which was just at the Limit of significance . Our data support the notion that Ca2+ can permeate cardiac Na+ chann els in the absence of an agonist and external Na+.