Abstract
Non-L-type calcium channels contribute to cerebrovascular function
Proceedings of the Australian Physiological Society, Vol.40, p.40P
Joint Meeting: Australian Neuroscience Society (ANS) and Australian Physiological Society (AuPS), 2010 (Sydney, Australia, 31-Jan-2010–03-Feb-2010)
2010
Abstract
Antagonists of L-type voltage dependent calcium channels (VDCCs) are widely used in the treatment of vasospasm following subarachnoid haemorrhage, howevertheir effectiveness in improving patient outcome is questionable. Our aim was to determine whether non-L-type calcium currents contribute to cerebrovascular function, and to determine the selectivity of T-type VDCC antagonists. Quantitative PCR, immunohistochemistry and immunoelectronmicroscopywere used to define the subtypes and location of voltage-dependent calcium channels expressed in cerebral arteries. Patch clamp electrophysiology,pressure myographyand pharmacology were used to classify calcium currents in isolated cerebrovascular SMCs and responses of cerebral arteries. Messenger RNAand protein for L- (CaV1.2) and T-type channels (CaV 3.1, CaV 3.2) were detected in cerebral arteries. In isolated SMCs, a high voltage-activated calcium current with L-type VDCC kinetics and sensitivity to the dihydropyridines, nifedipine and nimodipine, comprised 75% of the current, while the residual current had kinetics typical of T-type currents. Both the dihydropyridine-sensitive and insensitive components could be blocked by T-type blockers, but only the sensitive component was blocked by diltiazem. This component was larger in SMCs from smaller arteries. In large pressurised arteries, voltage-dependent constriction was abolished by L-type antagonists, while in smaller arteries, this required both L- and T-type antagonists. However, considerable overlap in the action of these antagonists was found. Wesuggest that aheterogeneous population of L-type and high voltage-activated T-type VDCCs contribute to vascular tone in resistance sized cerebral arteries, providing a noveltherapeutic target for therapy-resistant vasospasm.
Details
- Title
- Non-L-type calcium channels contribute to cerebrovascular function
- Authors
- I Y Kuo (Author) - Australian National UniversityV S Seymour (Author) - Australian National UniversityShaun L Sandow (Author) - University of New South WalesA Ellis (Author) - Australian National UniversityC E Hill (Author) - Australian National University
- Publication details
- Proceedings of the Australian Physiological Society, Vol.40, p.40P
- Conference details
- Joint Meeting: Australian Neuroscience Society (ANS) and Australian Physiological Society (AuPS), 2010 (Sydney, Australia, 31-Jan-2010–03-Feb-2010)
- Publisher
- Australian Physiological Society
- Date published
- 2010
- ISSN
- 0067-2084
- 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
- 99448833602621
- Output Type
- Abstract
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