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

1. Whole-cell patch clamp currents from freshly isolated adult rat ventricular cells, recorded in external Ca²⁺ (Ca(o)²⁺) but no external Na⁺ (Na(o)⁺), 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 Ni²⁺ and 10 μM La³⁺, but suppressed by 10 μM tetrodotoxin (TTX). We refer to this component as I(Ca(TTX)). 2. The conductance-voltage, g(V), relation in Ca(o)²⁺ only was well described by a single Boltzmann function (half-maximum potential, V( 1/4 ), of -44.5; slope factor, k, of -4.49 mV, means of 3 cells). g(V) in Ca(o)²⁺ plus Na(o)⁺ was better described as the sum of two Boltzmann functions, one nearly identical to that in Ca(o)²⁺ only (mean V( 1/4 ) of -45.1 and k of -3.90 mV), and one clearly distinct (mean V( 1/4 ) of -35.6 and k of -2.31 mV). Mean maximum conductance for I(Ca(TTX)) channels increased 23.7% on adding 1 mM Na₀⁺ to 3 mM Ca(o)²⁺. I(Ca(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 I(Ca(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.