TETRODOTOXIN-BLOCKABLE CALCIUM CURRENTS IN RAT VENTRICULAR MYOCYTES -A 3RD TYPE OF CARDIAC CELL SODIUM CURRENT

1. Whole-cell patch clamp currents from freshly isolated adult rat ven tricular cells, recorded in external Ca2+ (Ca-o(2+)) but no external N a+ (Na-o(+)), displayed two inward current components: a smaller compo nent that activated over more negative potentials and a larger compone nt (L-type Ca2+ current) that activated at more positive potentials. T he smaller component was not generated by Ca2+ channels. It was insens itive to 50 mu M Ni2+ and 10 mu M La3+, but suppressed by 10 mu M tetr odotoxin (TTX). We refer to this component as I-Ca(TTX).2. The conduct ance-voltage, g(V), relation in Ca-o(2+) only was well described by a single Boltzmann function (half-maximum potential, V-1/2, of -44.5; sl ope factor, k, of -4.49 mV, means of 3 cells). g(V) in Ca-o(2+) plus N a-o(+) was better described as the sum of two Boltzmann functions, one nearly identical to that in Cao(2+) only (mean V-1/2 of -45.1 and k o f -3.90 mV), and one clearly distinct (mean V-1/2 of -35.6 and k of -2 .31 mV). Mean maximum conductance for I-Ca(TTX) channels increased 23. 7% on adding 1 mM Na-o(+) to 3 mM Ca-o(2+). I-Ca(TTX) channels are per meable to Na+ ions, insensitive to Ni2+ and La3+ and blocked by TTX. T hey are Na+ channels. 3. I-Ca(TTX) channels are distinct from classica l cardiac Na+ channels. They activate and inactivate over a more negat ive range of potentials and have a slower time constant of inactivatio n than the classical Na+ channels. They are also distinct from yet ano ther rat ventricular Na+ current component characterized by a much hig her TTX sensitivity and by a persistent, non-fast-inactivating fractio n. That I-Ca(TTX) channels activate over a more negative range of pote ntials than classical cardiac Na+ channels suggests that they may be c ritical for triggering the ventricular action potential and so of impo rtance for cardiac arrhythmias.