Mechanisms underlying regional differences in the Ca2+ sensitivity of BKCa current in arteriolar smooth muscle

Yan Yang, Yoshiro Sohma, Zahra Nourian, Srikanth R. Ella, Min Li, Aaron Stupica, Ronald J. Korthuis, Michael J. Davis, Andrew P. Braun, Michael A. Hill

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

β1-Subunits enhance the gating properties of large-conductance Ca2+-activated K+ channels (BKCa) formed by α-subunits. In arterial vascular smooth muscle cells (VSMCs), β1-subunits are vital in coupling SR-generated Ca2+ sparks to BKCa activation, affecting contractility and blood pressure. Studies in cremaster and cerebral VSMCs show heterogeneity of BKCa activity due to apparent differences in the functional β1-subunit:α-subunit ratio. To define these differences, studies were conducted at the single-channel level while siRNA was used to manipulate specific subunit expression. β1 modulation of the α-subunit Ca2+ sensitivity was studied using patch-clamp techniques. BKCa channel normalized open probability (NPo) versus membrane potential (Vm) curves were more left-shifted in cerebral versus cremaster VSMCs as cytoplasmic Ca2+ was raised from 0.5 to 100 μm. Calculated V1/2 values of channel activation decreased from 72.0 ± 6.1 at 0.5 μm Ca2+i to -89 ± 9 mV at 100 μm Ca2+i in cerebral compared with 101 ± 10 to -63 ± 7 mV in cremaster VSMCs. Cremaster BKCa channels thus demonstrated an ∼2.5-fold weaker apparent Ca2+ sensitivity such that at a value of Vm of -30 mV, a mean value of [Ca2+]i of 39 μm was required to open half of the channels in cremaster versus 16 μm[Ca2+]i in cerebral VSMCs. Further, shortened mean open and longer mean closed times were evident in BKCa channel events from cremaster VSMCs at either -30 or 30 mV at any given [Ca2+]. β1-Subunit-directed siRNA decreased both the apparent Ca2+ sensitivity of BKCa in cerebral VSMCs and the appearance of spontaneous transient outward currents. The data are consistent with a higher ratio of β1-subunit:α-subunit of BKCa channels in cerebral compared with cremaster VSMCs. Functionally, this leads both to higher Ca2+ sensitivity and NPo for BKCa channels in the cerebral vasculature relative to that of skeletal muscle.

Original languageEnglish
Pages (from-to)1277-1293
Number of pages17
JournalJournal of Physiology
Volume591
Issue number5
DOIs
Publication statusPublished - 2013 Mar

ASJC Scopus subject areas

  • Physiology

Fingerprint Dive into the research topics of 'Mechanisms underlying regional differences in the Ca<sup>2+</sup> sensitivity of BK<sub>Ca</sub> current in arteriolar smooth muscle'. Together they form a unique fingerprint.

  • Cite this

    Yang, Y., Sohma, Y., Nourian, Z., Ella, S. R., Li, M., Stupica, A., Korthuis, R. J., Davis, M. J., Braun, A. P., & Hill, M. A. (2013). Mechanisms underlying regional differences in the Ca2+ sensitivity of BKCa current in arteriolar smooth muscle. Journal of Physiology, 591(5), 1277-1293. https://doi.org/10.1113/jphysiol.2012.241562