Modulation of the gating of unitary cardiac L-type Ca(2+) channels by conditioning voltage and divalent ions.
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.
Josephson
Ira R
IR
Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. josephsoni@grc.nia.nih.gov
Guia
Antonio
A
Lakatta
Edward G
EG
Stern
Michael D
MD
D000818:Animals; D001464:Barium / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry; D020746:Calcium Channels, L-Type / Q000737:chemistry* / Q000378:metabolism; D002478:Cells, Cultured; D004594:Electrophysiology; D007477:Ions; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D020746:Calcium Channels, L-Type; D007477:Ions; D001464:Barium; D002118:Calcium