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