Regulation of arterial tone by calcium-dependent K+ channels and ATP-sensitive K+ channels

Cardiovasc Drugs Ther. 1993 Aug;7 Suppl 3:605-10. doi: 10.1007/BF00877627.

Abstract

Resistance arteries depolarize and constrict to elevations in intravascular pressure. However, many of the molecular aspects of this phenomenon are not known. We present evidence that large conductance calcium-dependent potassium (KCa) channels, which are activated by intracellular calcium and membrane depolarization, play a fundamental role in regulating the degree of intravascular pressure-induced, myogenic tone. We found that blockers of KCa channels, charybdotoxin (CTX, < 100 nM) and TEA+ (< 0.5 mM), further depolarized pressurized arteries by as much as 12 mV and decreased diameter by up to 40%. CTX blocked KCa channels in outside-out patches from arterial smooth muscles with half-block constant of 10 nM and external TEA+ caused a flickery block, with a half-block constant of 200 microM. We propose that KCa channels serve as a negative feedback pathway to limit the degree of membrane depolarization and hence vasoconstriction to pressure. In contrast, CTX and TEA+ (< 1 mM) were without effect on membrane hyperpolarization and dilation to a wide variety of synthetic (cromakalim, pinacidil, diazoxide, minoxidil sulfate) and endogenous agents [calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide, an endothelial-derived hyperpolarizing factor]. Glibenclamide and low concentrations of external barium that inhibit ATP-sensitive potassium (KATP) channels, however, blocked the hyperpolarizations and dilations to these substances. We have identified KATP channels as well as high-affinity glibenclamide binding sites in arterial smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Arteries / drug effects
  • Arteries / physiology
  • Calcium / pharmacology*
  • Coronary Vessels / drug effects
  • Coronary Vessels / physiology*
  • Potassium Channels / drug effects
  • Potassium Channels / physiology*
  • Vasoconstriction / drug effects

Substances

  • Potassium Channels
  • Adenosine Triphosphate
  • Calcium