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

R. Aggarwal, S. R. Shorofsky, L. Goldman, C. W. Balke

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)353-369
Number of pages17
JournalJournal of Physiology
Volume505
Issue number2
DOIs
StatePublished - Dec 1 1997

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