Regulation of CaV3.1 channels by glucocorticoids

The activity of low voltage-activated Ca ²⁺ (Ca _V3) channels is tightly coupled to neurotransmitter and hormone secretion. Previous studies have shown that Ca _V3 channels are regulated by glucocorticoids (GCs), though the mechanism underlying channel regulation remains unclear. Here, using the pituitary GH ₃ cell line as a model, we investigated whether Ca _V3 channel expression is under the control of GCs, and if their actions are mediated by transcriptional and/or post-transcriptional mechanisms. RT-PCR and western blot analyses showed that Ca _V3.1 but not Ca _V3.2 and Ca _V3.3 channels is expressed in the GH ₃ cells, and patch clamp recordings confirmed that Ca ²⁺ currents through low voltage-activated channels were decreased after chronic treatment with GCs. Consistent with this, total plasma membrane expression of Ca _V3.1 protein as analyzed by cell-surface biotinylation assays and semi-quantitative western blotting was also down-regulated, while quantitative real-time RT-PCR analysis revealed a significant decrease of Ca _V3.1 mRNA expression in the treated cells. In contrast, patch-clamp recordings on HEK-293 cells stably expressing recombinant Ca _V3.1 channels showed that Ca ²⁺ currents were not affected by GC treatment. These results suggest that decreased transcription is a likely mechanism to explain the inhibitory actions of GCs on the functional expression of native Ca _V3.1 channels.