Tetrodotoxin‐blockable calcium currents in rat ventricular myocytes; a third type of cardiac cell sodium current

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Abstract
1 Whole‐cell patch clamp currents from freshly isolated adult rat ventricular cells, recorded in external Ca2+ (Ca2+o) but no external Na+ (Ma4o), displayed two inward current components: a smaller component that activated over more negative potentials and a larger component (L‐type Ca2+ current) that activated at more positive potentials. The smaller component was not generated by Ca2+ channels. It was insensitive to 50 μm M2+ and 10 μm La3+, but suppressed by 10 μm tetrodotoxin (TTX). We refer to this component as ICa(TTx). 2 The conductance–voltage, g(V), relation in Ca2+o only was well described by a single Boltzmann function (half‐maximum potential, V½, of –44.5; slope factor, k, of –4.49 mV, means of 3 cells). g(V) in Ca2+o plus Na4o was better described as the sum of two Boltzmann functions, one nearly identical to that in Ca2+o only (mean V½ of –45.1 and k of – 3.90 mV), and one clearly distinct (mean V½ of –35.6 and k of –2.31 mV). Mean maximum conductance for ICa(TTX) channels increased 23.7 % on adding 1 mm Na+o to 3 mm Ca2+o. ICa(TTx) channels are permeable to Na+ ions, insensitive to Ni2+ and La3+ and blocked by TTX. They are Na+ channels. 3 I Ca(TTx) channels are distinct from classical cardiac Na+ channels. They activate and inactivate over a more negative range of potentials and have a slower time constant of inactivation than the classical Na+ channels. They are also distinct from yet another rat ventricular Na+ current component characterized by a much higher TTX sensitivity and by a persistent, non‐fast‐inactivating fraction. That ICa(TTx) channels activate over a more negative range of potentials than classical cardiac Na+ channels suggests that they may be critical for triggering the ventricular action potential and so of importance for cardiac arrhythmias.