Regulation of L-type calcium channels in pituitary GH(4)C(1) cells by depolarization.
The neurosecretory anterior pituitary GH(4)C(1) 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 (+)-[(3)H]PN200-110 binding site density and (45)Ca(2+) uptake in these cells (). This study presents a functional analysis by electrophysiological techniques of short term regulation of L-type Ca(2+) channels in GH(4)C(1) cells by membrane depolarization. Depolarization of GH(4)C(1) cells by 50 mm K(+) rapidly reduced the barium currents through L-type calcium channels by approximately 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.
Peri
R
R
Department of Pharmacology and Toxicology, State University of New York at Buffalo, Buffalo, New York 14214-3000, USA.
Triggle
D J
DJ
Singh
S
S
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002460:Cell Line; D008564:Membrane Potentials; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000502:physiology*; D051381:Rats
D020746:Calcium Channels, L-Type