Mechanisms of beta-adrenergic stimulation of cardiac Ca2+ channels revealed by discrete-time Markov analysis of slow gating

S. Herzig, P. Patil, J. Neumann, C. M. Staschen, D. T. Yue

Research output: Contribution to journalArticlepeer-review

Abstract

Individual cardiac Ca2+ channels cycle slowly between a mode of gating in which the channel is available to open, and one in which the channel remains silent. The regulation of this multisecond cycling process by isoproterenol was investigated by single-channel recording and the development of a discrete-time Markov model that describes the slow switching among modes in terms of (de) phosphorylation reactions. The results provide evidence that isoproterenol increases Ca2+ channel activity by a reciprocal regulatory mechanism: not only is the phosphorylation rate of the channel increased, but also the dephosphorylation rate decreased. The discrete-time Markov formalism should prove useful as a general tool for understanding the mode switching demonstrated by a number of ionic channels.

Original languageEnglish (US)
Pages (from-to)1599-1612
Number of pages14
JournalBiophysical journal
Volume65
Issue number4
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Biophysics

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