Evidence both L-type and non-L-type voltage-dependent calcium channels contribute to cerebral artery vasospasm following loss of NO in the rat

Alister J McNeish, F J Altayo, C J Garland

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Abstract

We recently found block of NO synthase in rat middle cerebral artery caused spasm, associated with depolarizing oscillations in membrane potential (E-m) similar in form but faster in frequency (circa 1 Hz) to vasomotion. T-type voltage-gated Ca2+ channels contribute to cerebral myogenic tone and vasomotion, so we investigated the significance of T-type and other ion channels for membrane potential oscillations underlying arterial spasm. Smooth muscle cell membrane potential (E-m) and tension were measured simultaneously in rat middle cerebral artery. NO synthase blockade caused temporally coupled depolarizing oscillations in cerebrovascular E-m with associated vasoconstriction. Both events were accentuated by block of smooth muscle BKCa. Block of T-type channels or inhibition of Na+/K+-ATPase abolished the oscillations in E-m and reduced vasoconstriction. Oscillations in E-m were either attenuated or accentuated by reducing [Ca2+](o) or block of K-V, respectively. TRAM-34 attenuated oscillations in both E-m and tone, apparently independent of effects against K(Ca)3.1. Thus, rapid depolarizing oscillations in E-m and tone observed after endothelial function has been disrupted reflect input from T-type calcium channels in addition to L-type channels, while other depolarizing currents appear to be unimportant. These data suggest that combined block of T and L-type channels may represent an effective approach to reverse cerebral vasospasm.
Original languageEnglish
Pages (from-to)151-159
Number of pages9
JournalVascular Pharmacology
Volume53
Issue number3-4
DOIs
Publication statusPublished - Sep 2010

Keywords

  • cerebral vasospasm
  • nitric oxide
  • endothelial cell dysfunction
  • T-type calcium channels
  • K-channels

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