Temporal profile of potassium channel dysfunction in cerebrovascular smooth muscle after experimental subarachnoid haemorrhage.
The pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH) involves sustained contraction of arterial smooth muscle cells that is maximal 6-8 days after SAH. We reported that function of voltage-gated K+ (KV) channels was significantly decreased during vasospasm 7 days after SAH in dogs. Since arterial constriction is regulated by membrane potential that in turn is determined predominately by K+ conductance, the compromised K+ channel dysfunction may cause vasospasm. Additional support for this hypothesis would be demonstration that K+ channel dysfunction is temporally coincident with vasospasm. To test this hypothesis, SAH was created using the double haemorrhage model in dogs and smooth muscle cells from the basilar artery, which develops vasospasm, were isolated 4 days (early vasospasm), 7 days (during vasospasm) and 21 days (after vasospasm) after SAH and studied using patch-clamp electrophysiology. We investigated the two main K+ channels (KV and large-conductance voltage/Ca2+-activated (KCa) channels). Electrophysiologic function of KCa channels was preserved at all times after SAH. In contrast, function of KV channels was significantly decreased at all times after SAH. The decrease in cell size and degree of KV channel dysfunction was maximal 7 days after SAH. The results suggest that KV channel dysfunction either only partially contributes to vasospasm after SAH or that compensatory mechanisms develop that lead to resolution of vasospasm before KV channels recover their function.
Department of Surgery, University of Chicago Medical Center and Pritzker School of Medicine, Chicago 60637, USA.
Babak S
BS
Jahromi
Yasuo
Y
Aihara
Jinglu
J
Ai
Zhen-Du
ZD
Zhang
George
G
Weyer
Elena
E
Nikitina
Reza
R
Yassari
Khaled M
KM
Houamed
R Loch
RL
Macdonald
D000818:Animals; D001488:Basilar Artery / Q000473:pathology*; D002478:Cells, Cultured; D002533:Cerebral Angiography / Q000379:methods; D004195:Disease Models, Animal; D004285:Dogs; D004307:Dose-Response Relationship, Radiation; D004553:Electric Conductivity; D004558:Electric Stimulation / Q000379:methods; D008564:Membrane Potentials / Q000502:physiology / Q000528:radiation effects; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000503:physiopathology*; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000502:physiology*; D011897:Random Allocation; D013345:Subarachnoid Hemorrhage / Q000473:pathology*; D013997:Time Factors; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000473:pathology
D015221:Potassium Channels