Inhibition of voltage-gated calcium channels by sequestration of beta subunits
Inmaculada Cuchillo-Ibañez1, Marcos Aldea, Jacques Brocard
1Departamento de Farmacologi;a y Terapeutica, Facultad de Medicina, Universidad Autonoma de Madrid, 4, 28029, Arzobispo Morcillo, Spain.
Abstract:
The auxiliary Ca(v)beta subunit is essential for functional expression of high-voltage activated Ca(2+) channels. Here, we describe a lure sequence designed to sequester the Ca(v)beta subunits in transfected bovine chromaffin cells. This sequence is composed of the extracellular and transmembrane domains of the alpha chain of the human CD8, the I-II loop of Ca(v)2.1 subunit, and EGFP. We showed that expressing the CD8-I-II-EGFP sequence in chromaffin cells led to a >50% decrease in overall Ca(2+) current density. Although this decrease involved all the Ca(2+) channel types (L, N, P/Q, R), the proportion of each type supporting the remaining current was altered. A similar effect was observed after transfection when measuring the functional role of Ca(2+) channels in catecholamine release by chromaffin cells: global decrease of release and change of balance between the different channel types supporting it. Possible explanations for this apparent discrepancy are further discussed.
More Related Videos
Related Concept Videos
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Antihypertensive Drugs: Action of Calcium Channel Blockers
Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Overview of Secretory Vesicles
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
G-Protein Gated Ion Channels
Sensory organs,...


