Date of Award

12-2021

Document Type

Dissertation

Degree Name

Ph.D.

Department

Basic Medical Sciences

Committee Chair

Mark S. Taylor, Ph.D.

Abstract

Minute-to-minute regulation of intercellular calcium concentrations is essential to allow the uterus to phasically contract and relax in a manner required for delivery. A specific class of calcium-activated potassium (KCa2.3) channels has been strongly implicated in the negative feedback control of intracellular calcium levels. Overexpression of KCa2.3 channels compromises labor by diminishing uterine contractions. Pharmacologic positive modulation of KCa2.3 channels with the small molecule cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]amine(CyPPA), increases the calcium sensitivity of KCa2.3 channels and promotes membrane hyperpolarization through potassium efflux. Local coupling of plasma membrane channels, such as TRP and KCa, and internal store release channels is required for activation and regulates tone in multiple vessels. A similar relationship in human uterine tissue is proposed based on preliminary studies suggesting internal calcium stores play a role in KCa-dependent feedback. This study characterized spontaneous and CyPPA augmented contractions and the role of internal stores in the KCa feedback control of human myometrial contractions.

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Cell Biology Commons

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