Voltage-gated K+ channel dysfunction in myocytes from a dog model of subarachnoid hemorrhage.
Delayed cerebral vasospasm after subarachnoid hemorrhage is primarily due to sustained contraction of arterial smooth muscle cells. Its pathogenesis remains unclear. The degree of arterial constriction is regulated by membrane potential that in turn is determined predominately by K+ conductance (GK). Here, we identified the main voltage-gated K+ (Kv) channels contributing to outward delayed rectifier currents in dog basilar artery smooth muscle as Kv2 class through a combination of electrophysiological and pharmacological methods. Kv2 current density was nearly halved in vasospastic myocytes after subarachnoid hemorrhage (SAH) in dogs, and Kv2.1 and Kv2.2 were downregulated in vasospastic myocytes when examined by quantitative mRNA, Western blotting, and immunohistochemistry. Vasospastic myocytes were depolarized and had a smaller contribution of GK toward maintenance of their membrane potential. Pharmacological block of Kv current in control myocytes mimicked the depolarization observed in vasospastic arteries. The degree of membrane depolarization was found to be compatible with the amount of vasoconstriction observed after SAH. We conclude that Kv2 dysfunction after SAH contributes to the pathogenesis of delayed cerebral vasospasm. This may confer a novel target for treatment of delayed cerebral vasospasm.
Jahromi
Babak S
BS
Department of Surgery, University of Chicago Medical Center and Pritzker School of Medicine, Chicago, Illinois, USA.
Aihara
Yasuo
Y
Ai
Jinglu
J
Zhang
Zhen-Du
ZD
Nikitina
Elena
E
Macdonald
Robert Loch
RL
D000818:Animals; D001488:Basilar Artery / Q000473:pathology; D015153:Blotting, Western; D004285:Dogs; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000502:physiology; D032342:Muscle Cells / Q000378:metabolism*; D009130:Muscle, Smooth / Q000473:pathology; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000032:analysis; D051669:Shab Potassium Channels / Q000378:metabolism*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000503:physiopathology*; D020301:Vasospasm, Intracranial / Q000209:etiology* / Q000378:metabolism
D012333:RNA, Messenger; D051669:Shab Potassium Channels