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Originally published In Press as doi:10.1074/jbc.M102613200 on June 18, 2001
J. Biol. Chem., Vol. 276, Issue 34, 31667-31673, August 24, 2001
Regulation of L-type Calcium Channels in Pituitary
GH4C1 Cells by Depolarization*
Ravikumar
Peri ,
David J.
Triggle§, and
Satpal
Singh¶
From the Department of Pharmacology and Toxicology, State
University of New York at Buffalo, Buffalo, New York 14214-3000
The neurosecretory anterior pituitary
GH4C1 cells exhibit the high
voltage-activated dihydropyridine-sensitive L-type and the low
voltage-activated T-type calcium currents. The activity of L-type
calcium channels is tightly coupled to secretion of prolactin and other
hormones in these cells. Depolarization induced by elevated
extracellular K+ reduces the dihydropyridine
(+)-[3H]PN200-110 binding site density and
45Ca2+ uptake in these cells (22). This study
presents a functional analysis by electrophysiological techniques of
short term regulation of L-type Ca2+ channels in
GH4C1 cells by membrane depolarization.
Depolarization of GH4C1 cells by 50 mM K+ rapidly reduced the barium currents
through L-type calcium channels by ~70% and shifted the voltage
dependence of activation by 10 mV to more depolarized potentials.
Down-regulation depended on the strength of the depolarizing stimuli
and was reversible. The currents recovered to near control levels on
repolarization. Down-regulation of the calcium channel currents was
calcium-dependent but may not have been due to excessive
accumulation of intracellular calcium. Membrane depolarization by
voltage clamping and by veratridine also produced a down-regulation of
calcium channel currents. The down-regulation of the currents had an
autocrine component. This study reveals a calcium-dependent
down-regulation of the L-type calcium channel currents by depolarization.
*
This work was supported in part by grants from Bayer, Inc.,
and Astra-Zeneca Pharmaceuticals, and Grant GM-50779 from the National
Institutes of Health.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.
Present address: DuPont Pharmaceuticals Company, Experimental
Station, Route 141 and Henry Clay Rd., Wilmington, DE 19880.
§
Present address: School of Pharmacy and Pharmaceutical Sciences,
State University of New York at Buffalo, Buffalo, NY 14260.
¶
To whom correspondence should be addressed: Dept. of
Pharmacology and Toxicology, 102 Farber Hall, State University of New York at Buffalo, Buffalo, NY 14214-3000. Tel.: 716-645-3870; Fax: 716-645-3870; E-mail: singhs@acsu.buffalo.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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