Is there a role for T-type Ca2+ channels in regulation of vasomotor tone in mesenteric arterioles?
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.
Jensen
Lars Jørn
LJ
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
Holstein-Rathlou
Niels-Henrik
NH
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
D020747:Calcium Channels, T-Type; D002118:Calcium