Negative feedback and stochastic behavior in the opening and closing of single L-type Ca channels

David T. Yue

Research output: Contribution to journalConference article

Abstract

Calcium channels form a vital link in the control of essential processes like excitability, contraction and neurosecretion. To appreciate how Ca channels function in this capacity, a clear understanding of their opening and closing, or gating properties is fundamentally required. With the advent of the patch-clamp technique, which enables detection of gating events from single channels, there has been the hope over the past few years that Ca channel gating can be thoroughly understood at an elementary, stochastic level. Yet, major questions about Ca channel gating remain unanswered because of the complexities of Ca-facilitated inactivation, a prominent feature of many Ca channels whereby Ca entry through the channel pore appears to speed long-term closure, or inactivation of the channel. While the existence of this important physiological control feature is unmistakable, even some of the rudimentary properties of this negative feedback system remain unclear and present interesting theoretical challenges absent in many other ion channels. We have begun to explore the use of conditional open probability analysis (COPA) to probe for changes in single-channel gating properties as a function of prior Ca entry through cardiac L-type Ca channels. We calculate Poo(t,tj), defined as the chance that a channel is open at time t if it is known to be open at time tj. The decay timecourse of Poo(t,tj) gauges the gating structure of the channel at time tj, much as the impulse response of a dynamical process embodies the character of a system at a given time. COPA reveals that Ca entry during the openings of a single Ca channel produces alterations in gating that evolve over hundreds of milliseconds, consistent with an enzymatic basis for part of the negative feedback loop. We are currently using COPA to investigate the dynamic range of the feedback control, and the mechanisms underlying the modulation.

Original languageEnglish (US)
Pages (from-to)618-619
Number of pages2
JournalAnnals of biomedical engineering
Volume19
Issue number5
StatePublished - Dec 1 1991
Event1991 Annual Fall Meeting of the Biomedical Engineering Society - Charlottesville, VA, USA
Duration: Oct 12 1991Oct 14 1991

ASJC Scopus subject areas

  • Biomedical Engineering

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