CaV3.1 Channels Facilitate Calcium Wave Generation and Myogenic Tone Development in Mouse Mesenteric Arteries.

BackgroundThe myogenic response is the mechanism whereby intraluminal pressure elicits arterial constriction pursuant to the maintenance of tissue perfusion. Smooth muscle [Ca2+] is a key determinant of constriction, a process intimately tied to L-type (CaV1.2) Ca2+ channels. While important, other Ca2+ channels, in particular T-type, are expressed and could contribute to pressure regulation within defined voltage ranges. This study examined the role of one T-type Ca2+ channel using mesenteric arteries from C57BL/6 wild type and CaV3.1-/- mice. MethodsPatch-clamp electrophysiology, pressure myography, non-invasive blood pressure measurements and rapid Ca2+ imaging were employed to define the CaV3.1-/- phenotype relative to C57BL/6. Proximity ligation assay tested the closeness of CaV3.1 channels to inositol triphosphate receptors (IP3R). Nifedipine (0.3 M) and 2-APB (50 M) were used to block L-type Ca2+ channels and IP3Rs, respectively. ResultsInitial experiments confirmed the absence of CaV3.1 expression and whole-cell current in global deletion mice, a change that coincided with a reduction in systemic blood pressure. Mesenteric arteries from CaV3.1-/- mice produced less myogenic tone than C57BL/6, particularly at lower pressures (20-60 mmHg) where membrane potential is more hyperpolarized. This reduction in myogenic tone correlated with diminished Ca2+ wave generation in the CaV3.1-/- mice. These asynchronous events are dependent upon Ca2+ release from the sarcoplasmic reticulum which is insensitive to L-type Ca2+ channel blockade. A close physical association ( View larger version (44K): org.highwire.dtl.DTLVardef@1b3fe9forg.highwire.dtl.DTLVardef@11954borg.highwire.dtl.DTLVardef@607417org.highwire.dtl.DTLVardef@65964c_HPS_FORMAT_FIGEXP M_FIG C_FIG