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(Circulation Research. 1999;85:e33-e43.)
© 1999 American Heart Association, Inc.

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Molecular Cloning and Characterization of the Intermediate-Conductance Ca²⁺-Activated K⁺ Channel in Vascular Smooth Muscle

Relationship Between K_Ca Channel Diversity and Smooth Muscle Cell Function

Craig B. Neylon, Richard J. Lang, Ying Fu, Alex Bobik, Peter H. Reinhart

From the Department of Neurobiology (C.N., P.H.), Duke University Medical Center, Durham, NC; Baker Medical Research Institute (C.N., Y.F., A.B.), Victoria; and Department of Physiology (R.L.), Monash University, Victoria, Australia.

Correspondence to Dr Craig B. Neylon, Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, NC 27710. E-mail neylon{at}neuro.duke.edu

Abstract—Recent evidence suggests that functional diversity of vascular smooth muscle is produced in part by a differential expression of ion channels. The aim of the present study was to examine the role of Ca²⁺-activated K⁺ channels (K_Ca channels) in the expression of smooth muscle cell functional phenotype. We found that smooth muscle cells exhibiting a contractile function express predominantly large-conductance (200 pS) K_Ca (BK) channels. In contrast, proliferative smooth muscle cells express predominantly K_Ca channels exhibiting a much smaller conductance (32 pS). These channels are blocked by low concentrations of charybdotoxin (10 nmol/L) but, unlike BK channels, are insensitive to iberiotoxin (100 nmol/L). To determine the molecular identity of this K⁺ channel, we cloned a 1.9-kb cDNA from an immature-phenotype smooth muscle cell cDNA library. The cDNA contains an open reading frame for a 425 amino acid protein exhibiting sequence homology to other K_Ca channels, in particular with mIK1 and hIK1. Expression in oocytes gives rise to a K⁺-selective channel exhibiting intermediate-conductance (37 pS at -60 mV) and potent activation by Ca²⁺ (K_d 120 nmol/L). Thus, we have cloned and characterized the vascular smooth muscle intermediate-conductance K_Ca channel (SMIK), which is markedly upregulated in proliferating smooth muscle cells. The differential expression of these K_Ca channels in functionally distinct smooth muscle cell types suggests that K_Ca channels play a role in defining the physiological properties of vascular smooth muscle. The full text of this article is available at http://www.circresaha.org.

Key Words: molecular cloning • K⁺ channel • vascular smooth muscle • [Ca²⁺]_i • charybdotoxin

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