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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 Ca(2+) 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 BK(Ca). 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 [Ca(2+)](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 publication

DOI

10.1016/j.vph.2010.06.002

Type

Journal article

Journal

Vascul Pharmacol

Publication Date

09/2010

Volume

53

Pages

151 - 159

Keywords

Animals, Calcium Channels, L-Type, Calcium Channels, T-Type, In Vitro Techniques, Large-Conductance Calcium-Activated Potassium Channels, Male, Membrane Potentials, Middle Cerebral Artery, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Nitric Oxide, Nitric Oxide Synthase, Rats, Rats, Wistar, Vasoconstriction