Low voltage-activated calcium channels in vascular smooth muscle: T-type channels and AVP-stimulated calcium spiking.
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.
Brueggemann
Lioubov I
LI
Department of Medicine, Cardiovascular Institute, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Martin
Beverly L
BL
Barakat
John
J
Byron
Kenneth L
KL
Cribbs
Leanne L
LL
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D026901:Membrane Transport Proteins; D020748:Mibefradil / Q000494:pharmacology; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
C121855:CACNA1G protein, human; C479952:CACNA1H protein, human; C469757:CACNA1I protein, human; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D026901:Membrane Transport Proteins; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D020748:Mibefradil; D002118:Calcium