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Title: The physiological and pathophysiological role of voltage-gated Kv7 channels in the vasculature
Author: Jepps, Thomas
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2013
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This thesis focused 011 the role of voltage-gated K+ channels encoded by KCNQ genes (Kv 7 channell) in vascular smooth muscle. An array of techniques were employed including isometric tension recordings, the Langendorff isolated heart, quantitative polymerase chain reaction and Western blotting to investigate Kv 7 function and expression in normotensive and hypertensive rats and mice. With t.he aid of structurally different Kv7 activators and Kv7 blockers, this thesis elucidated an important role for Kv 7 channels in the regulation of vascular reactivity. Increasing concentrations of structurally disparate K" 7 activators (S- l , retigabine, lCA-27243 and BMS-204352) caused concentration-dependent relaxations in segments of aorta, mesenteric artery, and renal artery from normotensive rats and mice. In the Landendorff isolated-heart, the Ky 7 activators dose-dependently increased coronary perfusion with varying efficacies. These data suggest that KCNQ-encoded channels together with KCNE-encoded subunits, contribute La setting the resting membrane potential in vascular smooth muscle, and in doing so can prevent vasoconstriction. In blood vessels taken from hypertensive rats and hypertensive mice, the vasorelaxant effects of the Ky7 activators were impaired significantly, which was associated wil.h reduced Ky 7.4 protein expression in all vessels tested. The attenuation in Ky 7 function and decrease in Ky 7.4 expression across different vascular beds provides important impetus to our understanding of the pathology of hypertension. In contrast, Ky 7 function and Ky 7.4 expression was unaffected in the hypertensive rat cerebral arteries compared to the normotensive rat cerebral arteries. This thesis has identified K" 7 channels as important regulators of the smooth muscle tone in the vasculature and discovered a vessel-specific role for K" 7 channels in hypertension.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available