Biophys J, November 2002, p. 2575-2586, Vol. 83, No. 5

Modulation of the Gating of Unitary Cardiac L-Type Ca²⁺ Channels by Conditioning Voltage and Divalent Ions

Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224 USA

Although a considerable number of studies have characterized inactivation and facilitation of macroscopic L-type Ca²⁺ channel currents, the single channel properties underlying these important regulatory processes have only rarely been examined using Ca²⁺ ions. We have compared unitary L-type Ca²⁺ channel currents recorded with a low concentration of Ca²⁺ ions with those recorded with Ba²⁺ ions to elucidate the ionic dependence of the mechanisms responsible for the prepulse-dependent modulation of Ca²⁺ channel gating kinetics. Conditioning prepulses were applied across a wide range of voltages to examine their effects on the subsequent Ca²⁺ channel activity, recorded at a constant test potential. All recordings were made in the absence of any Ca²⁺ channel agonists. Moderate-depolarizing prepulses resulted in a decrease in the probability of opening of the Ca²⁺ channels during subsequent test voltage steps (inactivation), the extent of which was more dramatic with Ca²⁺ ions than Ba²⁺ ions. Facilitation, or increase of the average probability of opening with strong predepolarization, was due to long-duration mode 2 openings with Ca²⁺ ions and Ba²⁺ ions, despite a decrease in Ca²⁺ channel availability (inactivation) under these conditions. The degree of both prepulse-induced inactivation and facilitation decreased with increasing Ba²⁺ ion concentration. The time constants (and their proportions) describing the distributions of Ca²⁺ channel open times (which reflect mode switching) were also prepulse-, and ion-dependent. These results support the hypothesis that both prior depolarization and the nature and concentration of permeant ions modulate the gating properties of cardiac L-type Ca²⁺ channels.

Biophys J, November 2002, p. 2575-2586, Vol. 83, No. 5
© 2002 by the Biophysical Society   0006-3495/02/11/2575/12  $2.00

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