Modulation of the conductance of unitary cardiac L-type Ca(2+) channels
by conditioning voltage and divalent ions.
Biophys J, 83 (5):
2587--2594 (November 2002)Abstract
The accompanying paper (Josephson, I. R., A. Guia, E. G. Lakatta,
and M. D. Stern. 2002. Biophys. J. 83:2575-2586) examined the effects
of conditioning prepulses on the kinetics of unitary L-type Ca(2+)
channel currents using Ca(2+) and Ba(2+) ions to determine the ionic-dependence
of gating mechanisms responsible for channel inactivation and facilitation.
Here we demonstrate that in addition to alterations in gating kinetics,
the conductance of single L-type Ca(2+) channels was also dependent
on the prior conditioning voltage and permeant ions. All recordings
were made in the absence of any Ca(2+) channel agonists. Strongly
depolarizing prepulses produced an increased frequency of long-duration
(mode 2) openings during the test voltage steps. Mode 2 openings
also displayed >25\% larger single channel current amplitude (at
0 mV) than briefer (but well-resolved) mode 1 openings. The conductance
of mode 2 openings was 26 pS for 105 mM Ba(2+), 18 pS for 5 mM Ba(2+),
and 6 pS for 5 mM Ca(2+) ions; these values were 70\% greater than
the conductance of Ca(2+) channel openings of all durations (mode
1 and mode 2). Thus, the prepulse-driven shift into mode 2 gating
results in a longer-lived Ca(2+) channel conformation that, in addition,
displays altered permeation properties. These results, and those
in the accompanying paper, support the hypothesis that multiple aspects
of single L-type Ca(2+) channel behavior (gating kinetics, modal
transitions, and ion permeation) are interrelated and are modulated
by the magnitude of the conditioning depolarization and the nature
and concentration of the ions permeating the channel.
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