Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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




Journal article


Vascul Pharmacol

Publication Date





151 - 159


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