title: Identification of L- and T-type Ca2+ channels in rat cerebral arteries: role in myogenic tone development.
abstract: L-type Ca(2+) channels are broadly expressed in arterial smooth muscle cells, and their voltage-dependent properties are important in tone development. Recent studies have noted that these Ca(2+) channels are not singularly expressed in vascular tissue and that other subtypes are likely present. In this study, we ascertained which voltage-gated Ca(2+) channels are expressed in rat cerebral arterial smooth muscle and determined their contribution to the myogenic response. mRNA analysis revealed that the α(1)-subunit of L-type (Ca(v)1.2) and T-type (Ca(v)3.1 and Ca(v)3.2) Ca(2+) channels are present in isolated smooth muscle cells. Western blot analysis subsequently confirmed protein expression in whole arteries. With the use of patch clamp electrophysiology, nifedipine-sensitive and -insensitive Ba(2+) currents were isolated and each were shown to retain electrical characteristics consistent with L- and T-type Ca(2+) channels. The nifedipine-insensitive Ba(2+) current was blocked by mibefradil, kurtoxin, and efonidpine, T-type Ca(2+) channel inhibitors. Pressure myography revealed that L-type Ca(2+) channel inhibition reduced tone at 20 and 80 mmHg, with the greatest effect at high pressure when the vessel is depolarized. In comparison, the effect of T-type Ca(2+) channel blockade on myogenic tone was more limited, with their greatest effect at low pressure where vessels are hyperpolarized. Blood flow modeling revealed that the vasomotor responses induced by T-type Ca(2+) blockade could alter arterial flow by ∼20-50%. Overall, our findings indicate that L- and T-type Ca(2+) channels are expressed in cerebral arterial smooth muscle and can be electrically isolated from one another. Both conductances contribute to myogenic tone, although their overall contribution is unequal.
authors.affiliation: Hotchkiss Brain and Libin Cardiovascular Research Institute and Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada.
authors.forename: Rasha R
authors.initials: RR
authors.lastname: Abd El-Rahman
authors.forename: Osama F
authors.initials: OF
authors.lastname: Harraz
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Brett
authors.forename: Yana
authors.initials: Y
authors.lastname: Anfinogenova
authors.forename: Rania E
authors.initials: RE
authors.lastname: Mufti
authors.forename: Daniel
authors.initials: D
authors.lastname: Goldman
authors.forename: Donald G
authors.initials: DG
authors.lastname: Welsh
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002536:Cerebral Arteries / Q000378:metabolism; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D008564:Membrane Potentials; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009213:Myography; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: C504728:Cacna1c protein, rat; C500994:Cacna1g protein, rat; C509958:Cacna1h protein, rat; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D012333:RNA, Messenger