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Biophys J, November 2001, p. 2647-2659, Vol. 81, No. 5

ICa(TTX) Channels Are Distinct from Those Generating the Classical Cardiac Na+ Current

Ye Chen-Izu,* Qun Sha,* Stephen R. Shorofsky,* Shawn W. Robinson,* W. Gil Wier,dagger L. Goldman,dagger and C. William Balke*dagger

Departments of  *Medicine and  dagger Physiology, School of Medicine, University of Maryland, Baltimore, Maryland 21201 USA

The Na+ current component ICa(TTX) is functionally distinct from the main body of Na+ current, INa. It was proposed that ICa(TTX) channels are INa channels that were altered by bathing media containing Ca2+, but no, or very little, Na+. It is known that Na+-free conditions are not required to demonstrate ICa(TTX). We show here that Ca2+ is also not required. Whole-cell, tetrodotoxin-blockable currents from fresh adult rat ventricular cells in 65 mm Cs+ and no Ca2+ were compared to those in 3 mM Ca2+ and no Cs+ (i.e., ICa(TTX)). ICa(TTX) parameters were shifted to more positive voltages than those for Cs+. The Cs+ conductance-voltage curve slope factor (mean, -4.68 mV; range, -3.63 to -5.72 mV, eight cells) is indistinguishable from that reported for ICa(TTX) (mean, -4.49 mV; range, -3.95 to -5.49 mV). Cs+ current and ICa(TTX) time courses were superimposable after accounting for the voltage shift. Inactivation time constants as functions of potential for the Cs+ current and ICa(TTX) also superimposed after voltage shifting, as did the inactivation curves. Neither of the proposed conditions for conversion of INa into ICa(TTX) channels is required to demonstrate ICa(TTX). Moreover, we find that cardiac Na+ (H1) channels expressed heterologously in HEK 293 cells are not converted to ICa(TTX) channels by Na+-free, Ca2+-containing bathing media. The gating properties of the Na+ current through H1 and those of Ca2+ current through H1 are identical. All observations are consistent with two non-interconvertable Na+ channel populations: a larger that expresses little Ca2+ permeability and a smaller that is appreciably Ca2+-permeable.

Biophys J, November 2001, p. 2647-2659, Vol. 81, No. 5
© 2001 by the Biophysical Society   0006-3495/01/11/2647/13  $2.00


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