Thapsigargin inhibits voltage-activated calcium channels in adrenal glomerulosa cells

Abstract

Thapsigargin, an inhibitor of the microsomal Ca2+ pumps, has been extensively used to study the intracellular Ca2+ pool participating in the generation of the agonist-induced Ca2+ signal in various cell types. A dual effect of this agent was observed in bovine adrenal zona glomerulosa cells. At nanomolar concentrations, thapsigargin stimulated a sustained Ca2+ influx, probably resulting from Ca(2+)-store depletion. In contrast, when added at micromolar concentrations, thapsigargin prevented the rise in cytosolic free Ca2+ concentration ([Ca2+]c) induced by K+. This inhibitory effect of thapsigargin on voltage-activated Ca2+ channels was confirmed by measuring Ba2+ currents by the patch-clamp technique. Both low-threshold (T-type) and high-threshold (L-type) Ca2+ channels were affected by micromolar concentrations of thapsigargin. Analysis of the current-voltage relationship for T-type channels revealed that thapsigargin did not modify the sensitivity of these channels to the voltage, but decreased the maximal current flowing through the channels. In conclusion, thapsigargin appears to exert a dual effect on adrenal glomerulosa cells. At lower concentrations, this agent induces a sustained Ca2+ entry, whereas at higher concentrations it decreases [Ca2+]c by blocking voltage-activated Ca2+ channels.

Janus Kinase 2 and Calcium Are Required for Angiotensin II-dependent Activation of Steroidogenic Acute Regulatory Protein Transcription in H295R Human Adrenocortical Cells

“…Together these data indicate that Ang II-stimulated StAR promoter activity is not dependent upon reaching a threshold level of [Ca 2ϩ ] i . Previous studies reported Tg increased aldosterone production in both primary cultures of bovine and rat adrenal glomerulosa cells (5,39,40). However, a significant Tg response in bovine adrenal cells required 8 mM K ϩ in the medium, and our culture conditions had 4 mM K ϩ , which may account for the difference.…”

Signaling Events Leading to Crassulacean Acid Metabolism Induction in the Common Ice Plant

“…Dose dependency of the effects of thapsigargin on cytosolic free Ca 2ϩ concentrations has been observed in mammalian cells. At nanomolar concentrations, thapsigargin induced sustained Ca 2ϩ release, whereas at micromolar concentrations it decreased intracellular Ca 2ϩ concentrations by blocking voltage-activated channels (Rossier et al, 1993). Although thapsigargin treatments cannot differentiate between intra-and extracellular Ca 2ϩ sources, these results indicate that changes in intracellular Ca 2ϩ are likely to contribute to Ppc1 induction.…”

A characterization of muscarinic receptor‐mediated intracellular Ca2+ mobilization in cultured rat hippocampal neurones

“…Thapsigargin has been reported to inhibit voltage-gated Ca¥ channel (VGCC) activity (Rossier et al 1993); however, such an action remains to be demonstrated in central neurones (Simpson et al 1995). In the present investigation thapsigargin had no obvious inhibitory action on VGCC-mediated Ca¥ elevations at the doses used: exposure of cells to thapsigargin (2-10 ìÒ) in the presence of 25 mÒ K¤ often increased intracellular Ca¥ levels but never decreased them ( Fig.…”