Activation of BK channels in rat chromaffin cells requires summation of Ca2+ influx from multiple Ca2+ channels

Murali Prakriya*, Christopher J. Lingle

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Large-conductance Ca2+ and voltage-dependent K+ channels (BK channels) in many tissues require high Ca2+ concentrations for activation and therefore might be expected to be tightly coupled to Ca2+ channels. However, in most cases, little is known about the relative organization of the BK channels and the Ca2+ channels involved in their activation. We probed the nature of the organization of BK and Ca2+ channels in rat chromaffin cells by manipulating Ca2+ influx through Ca2+ channels and by altering cellular Ca2+ buffering using EGTA and bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). The results were analyzed to determine the distance between Ca2+ and BK channels that would be most consistent with the experimental data. Most BK channels are close enough to Ca2+ channels to be resistant to the buffering action of millimolar of EGTA, but are far enough to be inhibited by BAPTA. Analysis of the EGTA/BAPTA results suggests that BK channels are at a distance of 50 to 160 nm from Ca2+ channels. A model that assumes random distribution of Ca2+ and BK channels fails to account for the observed [Ca2+](i) detected by BK channels, suggesting that a specific mechanism may exist to mediate the functional coupling between these channels. Importantly, the effects of EGTA and BAPTA cannot be explained by assuming a one-to-one coupling between Ca2+ and BK channels. Rather, Ca2+ influx through a number of Ca2+ channels appears to act in concert to regulate the behavior of any individual BK channel. Thus differences in BK channel open probabilities may be explained by differences in the extent of Ca2+ domain overlap at the sites of individual BK channels.

Original languageEnglish (US)
Pages (from-to)1123-1135
Number of pages13
JournalJournal of neurophysiology
Volume84
Issue number3
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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