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Ketamine blocks Ca²⁺-activated K⁺ channels in rabbit cerebral arterial smooth muscle cells

¹Department of Physiology and Biophysics, ²Molecular Cell Physiology Research Group, College of Medicine, Inje University, Busan 614-735; and ³Department of Molecular Science and Technology/Life Science, Ajou University, Suwon 442-749, Korea

Submitted 3 March 2003 ; accepted in final form 16 May 2003

Although ketamine and Ca²⁺-activated K⁺ (K_Ca) channels have been implicated in the contractile activity regulation of cerebral arteries, no studies have addressed the specific interactions between ketamine and the K_Ca channels in cerebral arteries. The purpose of this study was to examine the direct effects of ketamine on K_Ca channel activities using the patch-clamp technique in single-cell preparations of rabbit middle cerebral arterial smooth muscle. We tested the hypothesis that ketamine modulates the K_Ca channel activity of the cerebral arterial smooth muscle cells of the rabbit. Vascular myocytes were isolated from rabbit middle cerebral arteries using enzymatic dissociation. Single K_Ca channel activities of smooth muscle cells from rabbit cerebral arteries were recorded using the patch-clamp technique. In the inside-out patches, ketamine in the micromolar range inhibited channel activity with a half-maximal inhibition of the ketamine conentration value of 83.8 ± 12.9 µM. The Hill coefficient was 1.2 ± 0.3. The slope conductance of the current-voltage relationship was 320.1 ± 2.0 pS between 0 and +60 mV in the presence of ketamine and symmetrical 145 mM K⁺. Ketamine had little effect on either the voltage-dependency or open- and closed-time histograms of K_Ca channel. The present study clearly demonstrates that ketamine inhibits K_Ca channel activities in rabbit middle cerebral arterial smooth muscle cells. This inhibition of K_Ca channels may represent a mechanism for ketamine-induced cerebral vasoconstriction.

ketamine; patch-clamp techniques

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