The Role of L- and T-type Ca2+ Channels in Rat Cerebral Arteries
Date
2013-12-04
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Abstract
The overall goal of this thesis was to identify which voltage-gated Ca2+ channels are expressed in rat cerebral arterial smooth muscle and to determine their contributions to myogenic tone regulation. We began by exploring which voltage-gated Ca2+ channels are expressed in cerebral arterial smooth muscle. A combination of molecular, electrophysiological and functional measurements revealed the presence of L- (CaV1.2) and T-type (CaV3.1 and CaV3.2) Ca2+ channel subtypes in rat cerebral arteries. Both types contribute to arterial tone development, although the contribution of the L-type channels to tone development is greater. We then investigated the role of a specific T-type Ca2+ channel subtype, CaV3.2, in cerebral arterial smooth muscle by functional assessment and a structural approach using immunohistochemistry, proximity ligation assay, electron-tomography, and immunogold labeling, combined with computational modeling and electrophysiological measurements. Results indicate that Ca2+ influx through CaV3.2 channels elicits dilation by activating ryanodine receptors and inducing Ca2+ sparks, localized events that activate BKCa channels. In conclusion this work provided evidence for the presence of different types of voltage-gated Ca2+ channels and provided evidence of their diverse functional roles in regulating myogenic tone in rat cerebral arteries. Overall, the conclusions indicate the importance of the different functional roles of voltage-gated Ca2+ channels, which have substantial physiological relevance to the function of the cerebral vasculature.
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Biology--Cell, Biology--Molecular, Physiology
Citation
Abd El-Rahman, R. (2013). The Role of L- and T-type Ca2+ Channels in Rat Cerebral Arteries (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28330