Regulation of L-type Calcium Channels in Pituitary GH₄C ₁ Cells by Depolarization

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.