Cole, WilliamZhong, Xi2013-04-292013-06-102013-04-292013Zhong, X. (2013). Identification of Novel Mechanisms for Myogenic Control of Cerebral Arterial Diameter (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26421http://hdl.handle.net/11023/637Myogenic control of cerebral arterial diameter plays a fundamental role in the maintenance of normal vascular resistance and blood flow in the brain. Myogenic control of cerebral artery diameter is achieved by inherent pressure-dependent mechanisms of Ca2+-CaM-MLCK activation, ROK-mediated Ca2+ sensitization and cytoskeleton reorganization. The findings presented in this thesis identify novel elements in these molecular mechanisms, including: (1) Kv9.3 subunits that co-assemble with Kv2.1 subunits to form ScTx1-sensitive channels that regulate Em, (2) Kv7.4-containing channels that also regulate Em, and (3) a cytoskeleton protein, VASP, that is involved in a dynamic process of actin polymerization in response to pressure elevation. Both Kv2.1/9.3 channels and Kv7.4-containing channels of cerebral myocytes were shown to contribute to native Kv currents in myogenic control of cerebral arterial diameter. Regulation of VASP phosphorylation in the process of cytoskeleton reorganization was shown to participate in the pressure-dependent myogenic response and NO-mediated vasodilation of cerebral arteries. In summary, these findings provide novel understanding of the basic molecular mechanisms that contribute to the precise control of vascular smooth muscle contractility, and provide potentially important insights for identification of dysfunctional mechanisms leading to abnormal arterial regulation in pathological conditions, as well as the development of therapeutic strategies to treat arterial dysfunction.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.PhysiologyCerebral ArteryMyogenic responseNO-mediated VasodilationPotassium ChannelCytoskeleton ReorganizationVASP Phosphorylationdoctoral thesishttp://dx.doi.org/10.11575/PRISM/26421