TY - JOUR
T1 - Evidence both L-type and non-L-type voltage-dependent calcium channels contribute to cerebral artery vasospasm following loss of NO in the rat
AU - McNeish, Alister J
AU - Altayo, F J
AU - Garland, C J
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - cerebral vasospasm
KW - nitric oxide
KW - endothelial cell dysfunction
KW - T-type calcium channels
KW - K-channels
UR - http://www.scopus.com/inward/record.url?scp=77956182675&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1016/j.vph.2010.06.002
U2 - 10.1016/j.vph.2010.06.002
DO - 10.1016/j.vph.2010.06.002
M3 - Article
SN - 1537-1891
VL - 53
SP - 151
EP - 159
JO - Vascular Pharmacology
JF - Vascular Pharmacology
IS - 3-4
ER -