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

Abstract

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