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(Stroke. 2009;40:1451.)
© 2009 American Heart Association, Inc.

Original Contributions

SK_Ca and IK_Ca Channels, Myogenic Tone, and Vasodilator Responses in Middle Cerebral Arteries and Parenchymal Arterioles

Effect of Ischemia and Reperfusion

Marilyn J. Cipolla, PhD; Jeremiah Smith, BS; Meghan M. Kohlmeyer, BS Julie A. Godfrey, BS

From the Departments of Neurology, OB/GYN & Reproductive Sciences, and Pharmacology (M.J.C., J.S., J.A.G.) and the Vermont Cancer Center (M.M.K.), University of Vermont College of Medicine, Burlington, Vt.

Correspondence to Marilyn J. Cipolla, PhD, University of Vermont, Department of Neurology, 89 Beaumont Avenue, Given C454, Burlington, VT 05405. E-mail Marilyn.Cipolla{at}uvm.edu

Background and Purpose— The role of SK_Ca and IK_Ca channels in myogenic tone and endothelium-derived hyperpolarizing factor (EDHF) responsiveness was investigated under control conditions and after ischemia and reperfusion in parenchymal arterioles (PA) versus middle cerebral arteries (MCA).

Methods— MCA and PA were dissected from male Wistar rats that were ischemic for 1 hour with 24 hours of reperfusion (n=12) or sham controls (n=12). Basal tone and reactivity to apamin (300 nmol/L), TRAM-34 (1.0 µmol/L), and nitro-L-arginine (0.1 mmol/L) were compared in PA and MCA pressurized to 40 mm Hg and 75 mm Hg, respectively. SK_Ca and IK_Ca channel mRNA expression was measured using real-time PCR.

Results— PA developed greater basal tone than MCA (42±4% versus 19±3%; P<0.01). Addition of apamin and TRAM-34 increased tone of PA by 25±3% and 16±2%, respectively, whereas MCA had no response to either inhibitor. After ischemia and reperfusion, the response to nitric oxide synthase inhibition (NOS) was diminished in PA, whereas EDHF responsiveness was preserved. In addition, stimulated EDHF dilation was partially reversed by apamin and completely reversed by TRAM-34 in both control and ischemic PA. SK_Ca and IK_Ca channel mRNA expression was similar in PA and MCA and not altered by ischemia and reperfusion. However, IK_Ca channel mRNA expression was 4- to 5-fold greater than SK_Ca channels.

Conclusions— It appears that SK_Ca and IK_Ca channel activity diminishes basal tone of PA, but not MCA. The preservation of EDHF responsiveness of PA after ischemia and reperfusion suggests an important role for this vasodilator under conditions when NOS is inhibited.

Key Words: ischemic stroke • parenchymal arterioles • potassium channels • vascular tone

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