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J. Biol. Chem., Vol. 277, Issue 25, 22119-22122, June 21, 2002
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-Subunit Can Interact
with and Modulate the Functional Properties of a Calcium-activated
Chloride Channel, CLCA1*
,
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
-subunits alter the kinetics and
increase the Ca2+ sensitivity of
Ca2+-dependent K+ channels (BK
channels) we investigated whether co-expression of
-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
-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.
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.
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