Low voltage-activated calcium channels in vascular smooth muscle: T-type channels and AVP-stimulated calcium spiking.
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Brueggemann LI, Martin BL, Barakat J, Byron KL, Cribbs LL
Low voltage-activated calcium channels in vascular smooth muscle: T-type channels and AVP-stimulated calcium spiking.
Am J Physiol Heart Circ Physiol. 2005 Feb;288(2):H923-35. Epub 2004 Oct 21.
- PubMed ID
- 15498818 [ View in PubMed]
- Abstract
An important path of extracellular calcium influx in vascular smooth muscle (VSM) cells is through voltage-activated Ca2+ channels of the plasma membrane. Both high (HVA)- and low (LVA)-voltage-activated Ca2+ currents are present in VSM cells, yet little is known about the relevance of the LVA T-type channels. In this report, we provide molecular evidence for T-type Ca2+ channels in rat arterial VSM and characterize endogenous LVA Ca2+ currents in the aortic smooth muscle-derived cell line A7r5. AVP is a vasoconstrictor hormone that, at physiological concentrations, stimulates Ca2+ oscillations (spiking) in monolayer cultures of A7r5 cells. The present study investigated the role of T-type Ca2+ channels in this response with a combination of pharmacological and molecular approaches. We demonstrate that AVP-stimulated Ca2+ spiking can be abolished by mibefradil at low concentrations (<1 microM) that should not inhibit L-type currents. Infection of A7r5 cells with an adenovirus containing the Cav3.2 T-type channel resulted in robust LVA Ca2+ currents but did not alter the AVP-stimulated Ca2+ spiking response. Together these data suggest that T-type Ca2+ channels are necessary for the onset of AVP-stimulated calcium oscillations; however, LVA Ca2+ entry through these channels is not limiting for repetitive Ca2+ spiking observed in A7r5 cells.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Mibefradil Voltage-dependent T-type calcium channel subunit alpha-1H Protein Humans YesInhibitorDetails