Molecular profile of vascular ion channels after experimental subarachnoid hemorrhage

J Cereb Blood Flow Metab. 2004 Jan;24(1):75-83. doi: 10.1097/01.WCB.0000095803.98378.D8.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Basilar Artery / anatomy & histology
  • Basilar Artery / physiology
  • Blood Vessels / metabolism*
  • Blotting, Western
  • Calcium Channels, L-Type / biosynthesis
  • Calcium Channels, L-Type / genetics
  • Coronary Vasospasm / metabolism
  • Delayed Rectifier Potassium Channels
  • Dogs
  • Gene Targeting
  • Ion Channels / metabolism*
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels / metabolism
  • Potassium Channels, Calcium-Activated / metabolism
  • Potassium Channels, Inwardly Rectifying*
  • Potassium Channels, Voltage-Gated*
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Subarachnoid Hemorrhage / metabolism*
  • Up-Regulation / physiology

Substances

  • Calcium Channels, L-Type
  • Delayed Rectifier Potassium Channels
  • Ion Channels
  • Kcnj10 (channel)
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Potassium Channels, Inwardly Rectifying
  • Potassium Channels, Voltage-Gated
  • RNA, Messenger