Beta-adrenergic stimulation of calcium channels occurs by potentiation of high-activity gating modes.

DT Yue, S Herzig, E Marban - Proceedings of the National …, 1990 - National Acad Sciences
Proceedings of the National Academy of Sciences, 1990National Acad Sciences
cAMP-dependent phosphorylation clearly increases current through cardiac L-type Ca
channels, but the molecular manifestation of this effect remains controversial. Previous work
implicates either an increase in the number of functional channels or graded changes in the
gating of individual channels. We now find that single cardiac Ca channels display three
patterns of activity (" modes") and that isoproterenol or 8-bromoadenosine 3', 5'-cyclic
monophosphate redistributes the relative proportions of modes such that the two most active …
cAMP-dependent phosphorylation clearly increases current through cardiac L-type Ca channels, but the molecular manifestation of this effect remains controversial. Previous work implicates either an increase in the number of functional channels or graded changes in the gating of individual channels. We now find that single cardiac Ca channels display three patterns of activity ("modes") and that isoproterenol or 8-bromoadenosine 3',5'-cyclic monophosphate redistributes the relative proportions of modes such that the two most active (mode 1, bursts of brief openings; mode 2, very long-lasting openings) are favored (P less than 0.05; n = 7). Conversely, a pattern of sparse brief openings (mode 0a) is selectively inhibited (P less than 0.01). Despite differences in the relative frequencies of the various modes before and during drug exposure, the gating within each mode is not detectably changed. We conclude that potentiation of highly active modes of Ca channel gating underlies the enhancement of calcium influx by beta-adrenergic stimulation.
National Acad Sciences