title: Molecular profile of vascular ion channels after experimental subarachnoid hemorrhage.
abstract: Cerebral vasospasm is a transient, delayed constriction of cerebral arteries that occurs after subarachnoid hemorrhage (SAH). Smooth muscle cells show impaired relaxation after SAH, which may be caused by a defect in the ionic mechanisms regulating smooth muscle membrane potential and Ca(2+) permeability. We tested this hypothesis by examining changes in expression of mRNA and protein for ion channels in the basilar arteries of dogs after SAH using quantitative real-time polymerase chain reaction (PCR) and western blotting. SAH was associated with a significant reduction in basilar artery diameter to 41 +/- 8% of pre-SAH diameter (P < 0.001) after 7 days. There was significant downregulation of the voltage-gated K(+) channel K(v) 2.2 (65% reduction in mRNA, P < 0.001; 49% reduction in protein, P < 0.05) and the beta1 subunit of the large-conductance, Ca(2+) - activated K(+) (BK) channel (53% reduction in mRNA, P < 0.02). There was no change in BK beta1 subunit protein. Changes in mRNA levels of K(v) 2.2 and the BK-beta1 subunit correlated with the degree of vasospasm (r(2) = 0.490 and 0.529 respectively, P < 0.05). The inwardly rectifying K(+) (K(ir)) channel K(ir) 2.1 was upregulated (234% increase in mRNA, P < 0.001; 350% increase in protein, P < 0.001). There was no significant change in mRNA expression of L- type Ca(2+) channels and the BK-alpha subunit. These data suggest that K(+) channel dysfunction may contribute to the pathogenesis of cerebral vasospasm.
authors.affiliation: Department of Surgery, University of Chicago and Pritzker School of Medicine, Chicago, IL 60637, USA.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Aihara
authors.forename: Babak S
authors.initials: BS
authors.lastname: Jahromi
authors.forename: Reza
authors.initials: R
authors.lastname: Yassari
authors.forename: Elena
authors.initials: E
authors.lastname: Nikitina
authors.forename: Mayowa
authors.initials: M
authors.lastname: Agbaje-Williams
authors.forename: R Loch
authors.initials: RL
authors.lastname: Macdonald
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000033:anatomy & histology / Q000502:physiology; D001808:Blood Vessels / Q000378:metabolism*; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000096:biosynthesis / Q000235:genetics; D003329:Coronary Vasospasm / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels; D004285:Dogs; D018390:Gene Targeting; D007473:Ion Channels / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013345:Subarachnoid Hemorrhage / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D000098854:Kcnj10 Channel
chemical_list: D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D007473:Ion Channels; D000098854:Kcnj10 Channel; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger