Non-l-type voltage-dependent calcium channels control vascular tone of the rat basilar artery

Manuel F. Navarro-Gonzalez, T. Hilton Grayson, Kate R. Meaney, Leanne L. Cribbs, Caryl E. Hill

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    28 Citations (Scopus)

    Abstract

    1. Constriction of cerebral arteries is considered to depend on L-type voltage-dependent calcium channels (VDCCs); however, many previous studies have used antagonists with potential non-selective actions. Our aim was to determine the expression and function of VDCCs in the rat basilar artery. 2. The relative expression of VDCC subtypes was assessed using quantitative polymerase chain reaction and immunohistochemistry. Data were correlated with physiological studies of vascular function. Domains I-II of the T channel subtypes expressed in the rat basilar artery were cloned and sequenced. 3. Blockade of L-type channels with nifedipine had no effect on vascular tone. In contrast, in the presence of nifedipine, hyperpolarization of short arterial segments produced relaxation, whereas depolarization of quiescent segments evoked constriction. 4. The mRNA and protein for L- and T-type VDCCs were strongly expressed in the main basilar artery and side branches, with CaV3.1 and Ca V1.2 the predominant subtypes. 5. T-Type VDCC blockers (i.e. 1 μmol/L mibefradil, 10 μmol/L pimozide and 100 μmol/L flunarizine) decreased intracellular calcium in smooth muscle cells, relaxed and hyperpolarized arteries, whereas nickel chloride (100 μmol/L) had no effect. In contrast with nifedipine, 10 μmol/L nimodipine produced hyperpolarization and relaxation. 6. When arteries were relaxed with 10 μmol/L U73122 (a phospholipase C inhibitor) in the presence of nifedipine, 40 mmol/L KCl evoked depolarization and constriction, which was significantly reduced by 1 μmol/L mibefradil. 7. Sequencing of domains I-II revealed splice variants of Ca V3.1, which may impact on channel activity. We conclude that vascular tone of the rat basilar artery results from calcium influx through nifedipine-insensitive VDCCs with pharmacology consistent with CaV3.1 T-type channels.

    Original languageEnglish
    Pages (from-to)55-66
    Number of pages12
    JournalClinical and Experimental Pharmacology and Physiology
    Volume36
    Issue number1
    DOIs
    Publication statusPublished - Jan 2009

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