Dihydropyridine-insensitive calcium currents contribute to function of small cerebral arteries

I Y Kuo; A Ellis; V A Seymour; Shaun L Sandow; C E Hill

doi:10.1038/jcbfm.2010.11

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Dihydropyridine-insensitive calcium currents contribute to function of small cerebral arteries

Journal article

Peer reviewed

Dihydropyridine-insensitive calcium currents contribute to function of small cerebral arteries

I Y Kuo, A Ellis, V A Seymour, Shaun L Sandow and C E Hill

Journal of Cerebral Blood Flow and Metabolism, Vol.30(6), pp.1226-1239

2010

DOI: https://doi.org/10.1038/jcbfm.2010.11

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Abstract

arterial size

calcium channels

cerebral vasoconstriction

dihydropyridines

T-type channels

Although dihydropyridines are widely used for the treatment of vasospasm, their effectiveness is questionable, suggesting that other voltage-dependent calcium channels (VDCCs) contribute to control of cerebrovascular tone. This study therefore investigated the role of dihydropyridine-insensitive VDCCs in cerebrovascular function. Using quantitative PCR and immunohistochemistry, we found mRNA and protein for L-type (CaV 1.2) and T-type (Ca V 3.1 and CaV 3.2) channels in adult rat basilar and middle cerebral arteries and their branches. Immunoelectron microscopy revealed both L-and T-type channels in smooth muscle cell (SMC) membranes. Using patch clamp electrophysiology, we found that a high-voltage-activated calcium current, showing T-type channel kinetics and insensitivity to nifedipine and nimodipine, comprised 20% of current in SMCs of the main arteries and 45% of current in SMCs from branches. Both components were abolished by the T-type antagonists mibefradil, NNC 55-0396, and efonidipine. Although nifedipine completely blocked vasoconstriction in pressurized basilar arteries, a nifedipine-insensitive constriction was found in branches and this increased in magnitude as vessel size decreased. We conclude that a heterogeneous population of VDCCs contributes to cerebrovascular function, with dihydropyridine-insensitive channels having a larger role in smaller vessels. Sensitivity of these currents to nonselective T-type channel antagonists suggests that these drugs may provide a more effective treatment for therapy-refractory cerebrovascular constriction. © 2010 ISCBFM All rights reserved.

Details

Title: Dihydropyridine-insensitive calcium currents contribute to function of small cerebral arteries
Authors: I Y Kuo (Author) - Australian National University
A Ellis (Author) - Australian National University
V A Seymour (Author) - Australian National University
Shaun L Sandow (Author) - University of New South Wales
C E Hill (Author) - Australian National University
Publication details: Journal of Cerebral Blood Flow and Metabolism, Vol.30(6), pp.1226-1239
Publisher: Nature Publishing Group
Date published: 2010
DOI: 10.1038/jcbfm.2010.11
ISSN: 0271-678X
Organisation Unit: School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99448897602621
Output Type: Journal article

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Collaboration types: Domestic collaboration
Web Of Science research areas: Endocrinology & Metabolism; Hematology; Neurosciences

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