I-Ca(TTX) channels are distinct from those generating the classical cardiac Na+ current

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 Ca2+, but no, or ve ry little, Na+. It is known that Na+-free conditions are not required to de monstrate I,au,,). 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., I-Ca(TTX). I-Ca(TTX) parameters were shifted to more positive voltages tha n those for Cs+. The Cs+ conductance-voltage curve slope factor (mean, -4.6 8 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+ cur rent and I-Ca(TTX) time courses were superimposable after accounting for th e 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 convers ion of I-Na into I-Ca(TTX) channels is required to demonstrate I-Ca(TTX). M oreover, we find that cardiac Na+ (H1) channels expressed heterologously in HEK 293 cells are not converted to I-Ca(TTX) channels by Na+-free, Ca2+-co ntaining bathing media. The gating properties of the Na+ current through H1 and those of Ca2+ current through H1 are identical. All observations are c onsistent with two non-interconvertable Na+ channel populations: a larger t hat expresses little Ca2+ permeability and a smaller that is appreciably Ca 2+-permeable.