90 Scopus citations

Abstract

Arterial smooth muscle from hypertensive rats shows an increased membrane permeability to K+ that depends on Ca2+ influx. To define the mechanism of this membrane alteration, we tested the hypothesis that Ca2+-dependent K+ current (I(K(Ca))) is increased in arterial muscle membranes from genetically hypertensive rats. Single-channel K+ currents measured in cell-attached and inside-out aortic membrane patches from spontaneously hypertensive rats (SHR) were compared with those from normotensive Wistar-Kyoto rats (WKY). Inside- out patches from both rat strains showed a predominant 225 pS, Ca2+- and voltage-dependent K+ channel in symmetrical 145 mM KCl solutions, which was blocked by tetraethylammonium [concentration for half-maximal block (IC50) ≤ 0.3 mM]. In cell-attached patches of aortic muscle cells bathed in physiological salt solution, this channel [I(K(Ca)) channel] showed a fivefold higher open-state probability (NP(o)) in SHR as compared with WKY. This increased NP(o) of SHR I(K(Ca)) channels in membranes of intact aortic muscle cells was not correlated with an altered membrane potential in current-clamped SHR myocytes or with changes in cytosolic free Ca2+ concentration in fura-2-loaded aortic muscle cells. However, inside-out aortic membrane patches from SHR showed more detected I(K(Ca)) channels per patch, a higher I(K(Ca)) channel NP(o), and a greater total patch current than their WKY counterparts. Further analysis revealed a greater Ca2+ sensitivity of SHR than WKY I(K(Ca)) channels. These results suggest that I(K(Ca)) channel function is altered in isolated membrane patches of arterial muscle from genetically hypertensive rats. It is possible that an augmented Ca2+ sensitivity of vascular muscle I(K(Ca)) channels provides a local counterregulatory mechanism to limit arterial muscle excitability and contraction in hypertension.

Original languageEnglish
Pages (from-to)H1337-H1345
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume264
Issue number5 33-5
DOIs
StatePublished - 1993

Keywords

  • calcium
  • hypertension
  • potassium channels
  • vascular smooth muscle

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