Tetramethrin

ABSTRACT The Na+ current component I^sub Ca(TTX)^ is functionally distinct from the main body of Na+ current, I^sub Na^. It was proposed that I^sub Ca(TTX)^ channels are I^sub Na^. channels that were altered by bathing media containing Ca^sup 2+^, but no, or very little, Na+. It is known that Na+-free conditions are not required to demonstrate I^sub Ca(TTX)^. We show here that Ca^sup 2+^ is also not required. Whole-cell, tetrodotoxin-blockable currents from fresh adult rat ventricular cells in 65 mm Cs+ and no Ca^sup 2+^ were compared to those in 3 mM Ca^sup 2+^ and no Cs+ (i.e., I^sub Ca(TTX)^). I^sub Ca(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 I^sub Ca(TTX)^ (mean, -4.49 mV; range, -3.95 to -5.49 mV). Cs+ current and I^sub Ca(TTX)^ time courses were superimposable after accounting for the voltage shift. Inactivation time constants as functions of potential for the Cs+ current and I^sub Ca(TTX)^ also superimposed after voltage shifting, as did the inactivation curves. Neither of the proposed conditions for conversion of I^sub Na^ into I^sub Ca(TTX)^ channels is required to demonstrate I^sub Ca(TTX)^. Moreover, we find that cardiac Na+ (H1) channels expressed heterologously in HEK 293 cells are not converted to I^sub Ca(TTX)^ channels by Na+-free, Ca^sup 2+^-containing bathing media. The gating properties of the Na+ current through H1 and those of Ca^sup 2+^ current through Hi are identical. All observations are consistent with two non-interconvertable Na+ channel populations: a larger that expresses little Ca^sup 2+^ permeability and a smaller that is appreciably Ca^sup 2+^-permeable.

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

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

Received for publication 9 February 2001 and in final form 19 July 2001.

Address reprint requests to: C. William Balke, M.D., Department of Physiology, University of Maryland School of Medicine, Howard Hall, Room 525, 660 West Redwood Street, Baltimore, MD 21201-1541. Tel.: 410-706-0515; Fax: 410-706-8610; E-mail: bbalke@medicine. umaryland.edu.

Copyright Biophysical Society Nov 2001
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