ArticleCirculation research2014
Ca(V)3.2 channels and the induction of negative feedback in cerebral arteries.
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Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
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Who cites it
49 citing papers in PubMed, 77 citations in OpenAlex.
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- A pericyte chloride clamp mechanism governs capillary control of cerebral blood flow.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Systems biology analysis of vasodynamics in mouse cerebral arterioles during resting state and functional hyperemia.PLoS computational biology · 2026Article
- TMEM16A channel signalling microdomains in the regulation of vascular function.The Journal of physiology · 2026Review
- Differential contribution of T-type voltage-gated calcium channels to vascular reactivity in the aorta and renal artery of healthy rabbits.Experimental physiology · 2026Article
- Sex-specific modulation of T-type voltage-gated calcium channels in the renal artery of hypertensive rats.Frontiers in physiology · 2026Article
- Roles of G-protein coupled receptors and mechanosensitive ion channels in pressure-induced chronotropy of lymphatic vessels.bioRxiv : the preprint server for biology · 2025Article
- The machinery of healthy vasodilatation: an overview.Pflugers Archiv : European journal of physiology · 2025Review
- Functional, Structural and Proteomic Effects of Ageing in Resistance Arteries.International journal of molecular sciences · 2024Review
- Electro-metabolic signaling.The Journal of general physiology · 2024Article
- Long-term hypoxia modulates depolarization activation of BKFrontiers in physiology · 2024Article
- The conducted vasomotor response and the principles of electrical communication in resistance arteries.Physiological reviews · 2024Review
- CaScientific reports · 2023Article
- Impact of aging on vascular ion channels: perspectives and knowledge gaps across major organ systems.American journal of physiology. Heart and circulatory physiology · 2023Review
- Vascular mechanotransduction.Physiological reviews · 2023Review
- Ion channel molecular complexes in vascular smooth muscle.Frontiers in physiology · 2022Review
- Vascular calcium signalling and ageing.The Journal of physiology · 2021Review
- Gestational long-term hypoxia induces metabolomic reprogramming and phenotypic transformations in fetal sheep pulmonary arteries.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- The Calcium Signaling Mechanisms in Arterial Smooth Muscle and Endothelial Cells.Comprehensive Physiology · 2021Article
- Cerebrovascular and neurological perspectives on adrenoceptor and calcium channel modulating pharmacotherapies.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
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Authors and funding
20 authors at 6 institutions in 3 countries.
Osama F HarrazFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Rasha R Abd El-RahmanFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Kamran Bigdely-ShamlooFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Sean M WilsonFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Suzanne E BrettFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Monica RomeroFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Albert L GonzalesFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Scott EarleyFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Edward J VigmondFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Anders NygrenFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Bijoy K MenonFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Rania E MuftiFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Tim WatsonFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Yves StarreveldFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Tobias FurstenhauptFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Philip R MuellerleileFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
David T KurjiakaFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Barry D KyleFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Andrew P BraunFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.).
Donald G WelshFrom the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes (O.F.H., R.R.A.E.-R., K.B.-S., S.E.B., R.E.M., B.D.K., A.P.B., D.G.W.), Department of Electrical and Computer Engineering (K.B.-S., E.J.V., A.N.), Department of Clinical Neurosciences (B.K.M., T.W., Y.S.), and Microscopy Imaging Facility (T.F.), University of Calgary, Calgary, Alberta, Canada; Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt (O.F.H.); Division of Pharmacology, Loma Linda University, CA (S.M.W., M.R.); Department of Biomedical Sciences, Colorado State University, Fort Collins (A.L.G.); Department of Pharmacology, University of Nevada, Reno (S.E.); LIRYC Institute and Lab IMB, University of Bordeaux, Bordeaux, France (E.J.V.); and Department of Biomedical Sciences, Grand Valley State University, Allendale, MI (P.R.M., D.T.K.). dwelsh@ucalgary.
Colorado State University · USInstitut de Mathématiques de Bordeaux · FRUniversity of Nevada, Reno · USAlexandria University · EGLoma Linda University · USUniversité de Bordeaux · FR
Funding
TRP Channel-Dependent Regulation of Arterial Tone (Renewal)R01HL091905 · NHLBI · UNIVERSITY OF NEVADA RENO · PI EARLEY, SCOTT · 2009 to 2020
$5.1MIntrauterine chronic hypoxia and ryanodine receptors in fetal pulmonary arteriesR03HD069746 · NICHD · LOMA LINDA UNIVERSITY · PI WILSON, SEAN M · 2012 to 2013
$145kCIHR MOP-69088NHLBI NIH HHS R01 HL091905NICHD NIH HHS HD069746NICHD NIH HHS R03 HD069746
Abstract
rationaleT-type (CaV3.1/CaV3.2) Ca(2+) channels are expressed in rat cerebral arterial smooth muscle. Although present, their functional significance remains uncertain with findings pointing to a variety of roles.
objectiveThis study tested whether CaV3.2 channels mediate a negative feedback response by triggering Ca(2+) sparks, discrete events that initiate arterial hyperpolarization by activating large-conductance Ca(2+)-activated K(+) channels. METHODS AND
resultsMicromolar Ni(2+), an agent that selectively blocks CaV3.2 but not CaV1.2/CaV3.1, was first shown to depolarize/constrict pressurized rat cerebral arteries; no effect was observed in CaV3.2(-/-) arteries. Structural analysis using 3-dimensional tomography, immunolabeling, and a proximity ligation assay next revealed the existence of microdomains in cerebral arterial smooth muscle which comprised sarcoplasmic reticulum and caveolae. Within these discrete structures, CaV3.2 and ryanodine receptor resided in close apposition to one another. Computational modeling revealed that Ca(2+) influx through CaV3.2 could repetitively activate ryanodine receptor, inducing discrete Ca(2+)-induced Ca(2+) release events in a voltage-dependent manner. In keeping with theoretical observations, rapid Ca(2+) imaging and perforated patch clamp electrophysiology demonstrated that Ni(2+) suppressed Ca(2+) sparks and consequently spontaneous transient outward K(+) currents, large-conductance Ca(2+)-activated K(+) channel mediated events. Additional functional work on pressurized arteries noted that paxilline, a large-conductance Ca(2+)-activated K(+) channel inhibitor, elicited arterial constriction equivalent, and not additive, to Ni(2+). Key experiments on human cerebral arteries indicate that CaV3.2 is present and drives a comparable response to moderate constriction.
conclusionsThese findings indicate for the first time that CaV3.2 channels localize to discrete microdomains and drive ryanodine receptor-mediated Ca(2+) sparks, enabling large-conductance Ca(2+)-activated K(+) channel activation, hyperpolarization, and attenuation of cerebral arterial constriction.
Indexed as
Calcium SignalingAnimalsCalcium Channels, T-TypeCerebral ArteriesFeedback, PhysiologicalFemaleLarge-Conductance Calcium-Activated Potassium ChannelsMembrane PotentialsMuscle, Smooth, VascularMyocytes, Smooth MuscleRatsRats, Sprague-DawleyRyanodine Receptor Calcium Release ChannelSarcoplasmic ReticulumCacna1g protein, ratCacna1h protein, ratCalcium Channels, T-TypeLarge-Conductance Calcium-Activated Potassium ChannelsRyanodine Receptor Calcium Release Channelcalcium channelscalcium channels, T-typecalcium signalingcerebral arteriesmuscle, smooth, vascularpotassium channels, calcium-activatedvasodilation
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