Endothelial SK(Ca) and IK(Ca) channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow

J Cereb Blood Flow Metab. 2011 May;31(5):1175-86. doi: 10.1038/jcbfm.2010.214. Epub 2010 Dec 22.

Abstract

Calcium-sensitive potassium (K(Ca)) channels have been shown to modulate the diameter of cerebral pial arteries; however, little is known regarding their roles in controlling cerebral parenchymal arterioles (PAs). We explored the function and cellular distribution of small-conductance (SK(Ca)) and intermediate-conductance (IK(Ca)) K(Ca) channels and large-conductance K(Ca) (BK(Ca)) channels in endothelial cells (ECs) and smooth muscle cells (SMCs) of PAs. Both SK(Ca) and IK(Ca) channels conducted the outward current in isolated PA ECs (current densities, ~20 pA/pF and ~28 pA/pF at +40 mV, respectively), but these currents were not detected in PA SMCs. In contrast, BK(Ca) currents were prominent in PA SMCs (~154 pA/pF), but were undetectable in PA ECs. Pressurized PAs constricted to inhibition of SK(Ca) (~16%) and IK(Ca) (~16%) channels, but were only modestly affected by inhibition of BK(Ca) channels (~5%). Blockade of SK(Ca) and IK(Ca) channels decreased resting cortical cerebral blood flow (CBF) by ~15%. NS309 (6,7-dichloro-1H-indole-2,3-dione3-oxime), a SK(Ca)/IK(Ca) channel opener, hyperpolarized PA SMCs by ~27 mV, maximally dilated pressurized PAs, and increased CBF by ~40%. In conclusion, these data show that SK(Ca) and IK(Ca) channels in ECs profoundly modulate PA tone and CBF, whereas BK(Ca) channels in SMCs only modestly influence PA diameter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterioles / metabolism*
  • Brain / blood supply*
  • Brain / metabolism
  • Cerebrovascular Circulation / physiology*
  • Electrophysiology
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism*
  • Fluorescent Antibody Technique
  • Male
  • Membrane Potentials / physiology
  • Microelectrodes
  • Muscle, Smooth, Vascular / metabolism
  • Potassium Channels, Calcium-Activated / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Vasodilation / physiology

Substances

  • Potassium Channels, Calcium-Activated