Functional coupling of the β1 subunit to the large conductance ca2+- activated K+ channel in the absence of Ca2+ increased Ca2+ sensitivity from a Ca2+-independent mechanism

Crina M. Nimigean, Karl L. Magleby

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Coexpression of the β1 subunit with the α subunit (mSlo) of BK channels increases the apparent Ca2+ sensitivity of the channel. This study investigates whether the mechanism underlying the increased Ca2+ sensitivity requires Ca2+, by comparing the gating in 0 Ca2+(i) of BK channels composed of α subunits to those composed of αβ1 subunits. The β1 subunit increased burst duration ~20-fold and the duration of gaps between bursts ~3-fold, giving an ~10-fold increase in open probability (P(o)) in 0 Ca2+(i). The effect of the β1 subunit on increasing burst duration was little changed over a wide range of P(o) achieved by varying either Ca2+(i) or depolarization. The effect of the β1 subunit on increasing the durations of the gaps between bursts in 0 Ca2+(i) was preserved over a range of voltage, but was switched off as Ca2+(i) was increased into the activation range. The Ca2+-independent, β1 subunit- induced increase in burst duration accounted for 80% of the leftward shift in the P(o) vs. Ca2+(i) curve that reflects the increased Ca2+ sensitivity induced by the β1 subunit. The Ca2+-dependent effect of the β1 subunit on the gaps between bursts accounted for the remaining 20% of the leftward shift. Our observation that the major effects of the β1 subunit are independent of Ca2+(i) suggests that the β1 subunit mainly alters the energy barriers of Ca2+-independent transitions. The changes in gating induced by the β1 subunit differ from those induced by depolarization, as increasing P(o) by depolarization or by the β1 subunit gave different gating kinetics. The complex gating kinetics for both α and α+β1 channels in 0 Ca2+(i)arise from transitions among two to three open and three to five closed states and are inconsistent with MonodWyman-Changeux type models, which predict gating among only one open and one closed state in 0 Ca2+(i).

Original languageEnglish (US)
Pages (from-to)719-734
Number of pages16
JournalJournal of General Physiology
Volume115
Issue number6
DOIs
StatePublished - Jun 2000

Keywords

  • K(Ca) channel
  • Maxi-K channel
  • Monod-Wyman-Changeux
  • MSlo
  • Single-channel

ASJC Scopus subject areas

  • Physiology

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