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Small‐ and Intermediate‐Conductance Calcium‐Activated K + Channels Provide Different Facets of Endothelium‐Dependent Hyperpolarization in Rat Mesenteric Artery
Author(s) -
Crane G. J.,
Gallagher N.,
Dora K. A.,
Garland C. J.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.051896
Subject(s) - hyperpolarization (physics) , apamin , cyclopiazonic acid , iberiotoxin , membrane potential , depolarization , biophysics , mesenteric arteries , chemistry , charybdotoxin , endothelium derived hyperpolarizing factor , channel blocker , medicine , endocrinology , potassium channel , biology , calcium , biochemistry , endoplasmic reticulum , stereochemistry , artery , nuclear magnetic resonance spectroscopy
Activation of both small‐conductance (SK Ca ) and intermediate‐conductance (IK Ca ) Ca 2+ ‐activated K + channels in endothelial cells leads to vascular smooth muscle hyperpolarization and relaxation in rat mesenteric arteries. The contribution that each endothelial K + channel type makes to the smooth muscle hyperpolarization is unknown. In the presence of a nitric oxide (NO) synthase inhibitor, ACh evoked endothelium and concentration‐dependent smooth muscle hyperpolarization, increasing the resting potential (approx. −53 mV) by around 20 mV at 3 μ m . Similar hyperpolarization was evoked with cyclopiazonic acid (10 μ m , an inhibitor of sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA)) while 1‐EBIO (300 μ m , an IK Ca activator) only increased the potential by a few millivolts. Hyperpolarization in response to either ACh or CPA was abolished with apamin (50 n m , an SK Ca blocker) but was unaltered by 1‐[(2‐chlorophenyl) diphenylmethyl]‐1H‐pyrazole (1 μ m TRAM‐34, an IK Ca blocker). During depolarization and contraction in response to phenylephrine (PE), ACh still increased the membrane potential to around −70 mV, but with apamin present the membrane potential only increased just beyond the original resting potential ( circa −58 mV). TRAM‐34 alone did not affect hyperpolarization to ACh but, in combination with apamin, ACh‐evoked hyperpolarization was completely abolished. These data suggest that true endothelium‐dependent hyperpolarization of smooth muscle cells in response to ACh is attributable to SK Ca channels, whereas IK Ca channels play an important role during the ACh‐mediated repolarization phase only observed following depolarization.