Search

Melanotrope cells of Xenopus laevis generate transitory increases in intracellular Ca(2+), known as Ca(2+) oscillations. These oscillations arise from the influx of Ca(2+) through voltage-operated Ca(2+) channels (VOCCs). Such oscillations are the driving force for secretion of a-melanophore-stimulating hormone (alpha-MSH) from the cell. The influx of Ca(2+) through VOCCs initiates the mobilization of intracellular Ca(2+) to generate a Ca(2+) wave. The function of the Ca(2+) wave in the melanotrope is unknown, but its presence in the nucleus suggests a role in the regulation of gene expression, perhaps that of proopiomelanocortin (POMC), the precursor protein for alpha-MSH. To determine the possible function of Ca(2+) waves in Xenopus melanotropes, we addressed whether functional VOCCs, which are an established requirement for both secretion and Ca(2+) wave initiation, are also required to maintain POMC gene expression.

The 1,4-dihydropyridine-sensitive voltage-gated Ca2+ channel is widely distributed in excitable cells. The channel and its several associated drug binding sites are known to be up- and downregulated by a variety of homologous and heterologous influences including membrane depolarization. The neurosecretory GH4C1 cell line possesses L-type channels. Depolarization of these cells by elevated K+ increases the binding affinity of 1,4-dihydropyridines and decreases the number of 1,4-dihydropyridine binding sites and functional channels. There is a coordinate upregulation of the number of muscarinic receptors. This membrane potential- and Ca(2+)-calmodulin-dependent process of channel downregulation may involve internalization of the channel heteromeric complex or, more plausibly, a dissociation of the complex and a concomitant loss of both binding and permeation functions.