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Originally published In Press as doi:10.1074/jbc.C200215200 on May 6, 2002

J. Biol. Chem., Vol. 277, Issue 25, 22119-22122, June 21, 2002
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ACCELERATED PUBLICATION
The Large Conductance Potassium Channel beta -Subunit Can Interact with and Modulate the Functional Properties of a Calcium-activated Chloride Channel, CLCA1*

Iain A. GreenwoodDagger , Lisa J. Miller, Susumu Ohya, and Burton Horowitz§

From the Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557-0046

We have recently compared the biophysical and pharmacological properties of native Ca2+-activated Cl- currents in murine portal vein with mCLCA1 channels cloned from murine portal vein myocytes (Britton, F. C., Ohya, S., Horowitz, B., and Greenwood, I. A. (2002) J. Physiol. (Lond.) 539, 107-117). These channels shared a similar relative permeability to various anions, but the expressed channel current lacked the marked time dependence of the native current. In addition, the expressed channel showed a lower Ca2+ sensitivity than the native channel. As non-pore-forming regulatory beta -subunits alter the kinetics and increase the Ca2+ sensitivity of Ca2+-dependent K+ channels (BK channels) we investigated whether co-expression of beta -subunits with CLCA1 would alter the kinetics/Ca2+ sensitivity of mCLCA1. Internal dialysis of human embryonic kidney cells stably expressing CLCA1 with 500 nM Ca2+ evoked a significantly larger current when the beta -subunit KCNMB1 was co-expressed. In a small number of co-transfected cells marked time dependence to the activation kinetics was observed. Interaction studies using the mammalian two-hybrid technique demonstrated a physical association between CLCA1 and KCNMB1 when co-expressed in human embryonic kidney cells. These data suggest that activation of CLCA1 can be modified by accessory subunits.


* This work was supported by National Institutes of Health Grants DK 41315, HL 49254, and P20 RR15581.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger A Wellcome Trust research fellow.

§ To whom reprint requests should be addressed: Dept. of Physiology and Cell Biology, University of Nevada School of Medicine, MS352/Anderson Medical Bldg., Reno, NV 89557-0046. Tel.: 775-784-1462; Fax: 775-784-6903; E-mail: burt@physio.unr.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.