title: Is there a role for T-type Ca2+ channels in regulation of vasomotor tone in mesenteric arterioles?
abstract: The largest peripheral blood pressure drop occurs in terminal arterioles (<40 microm lumen diameter). L-type voltage-dependent Ca2+ channels (VDCCs) are considered the primary pathway for Ca2+ influx during physiologic activation of vascular smooth muscle cells (VSMC). Recent evidence suggests that T-type VDCCs are expressed in renal afferent and efferent arterioles, mesenteric arterioles, and skeletal muscle arterioles. T-type channels are small-conductance, low voltage-activated, fast-inactivating channels. Thus, their role in supplying Ca2+ for contraction of VSMC has been disputed. However, T-type channels display non-inactivating window currents, which may play a role in sustained Ca2+ entry. Here, we review the possible role of T-type channels in vasomotor tone regulation in rat mesenteric terminal arterioles. The CaV3.1 channel was immunolocalized in VSMC, whereas the CaV3.2 channel was predominantly expressed in endothelial cells. Voltage-dependent Ca2+ entry was inhibited by the new specific T-type blockers R(-)-efonidipine and NNC 55-0396. The effect of NNC 55-0396 persisted in depolarized arterioles, suggesting an unusually high activation threshold of mesenteric T-type channels. T-type channels were not necessary for conduction of vasoconstriction, but appear to be important for local electromechanical coupling in VSMC. The first direct demonstration of endothelial T-type channels warrants new investigations of their role in vascular biology.
authors.affiliation: Division of Renal and Vascular Research, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. llj@mfi.ku.dk
authors.forename: Lars Jørn
authors.initials: LJ
authors.lastname: Jensen
authors.forename: Niels-Henrik
authors.initials: NH
authors.lastname: Holstein-Rathlou
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D008638:Mesenteric Arteries / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D014661:Vasoconstriction
chemical_list: D020747:Calcium Channels, T-Type; D002118:Calcium