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Date of Award

6-1989

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

Supervisor

M.S. Kannan

Abstract

This work intended to study cell membrane properties of cells from genetically hypertensive animals in culture. The spontaneously hypertensive rat from the Wistar-Kyoto strain (SH rats) was used as a model. Genetically related Wistar-Kyoto (WKY) and unrelated Spague-Dawley (SD) rats were used as controls. Neurones from the Superior Cervical Ganglia (SCG) were cultured in vitro, with and without target cells from the vasculature (aorta, A VSMC, and mesenteric artery, MA VSMC). Passive and active membrane electrical properties from SCG neurones and A and MA VSMC were studied with microelectrodes via injection of long-duration (400 msec.) depolarizing and hyperpolarizing square pulses of current.

Most of WKY and SD SCG neurones fired one or two action potentials upon depolarization. The majority of SH SCG neurones was found to have lost their accommodative properties and fired three or more action potentials upon depolarisation. In all strains, firing abilities were inhibited in presence of A VSMC. The firing frequencies distributions remained unchanged in SD and WKY cocultures, but was shifted to lower values in the presence of MA VSMC in SH co-cultures. Multiple firing was found to be initiated by the absence of or lack of activation of a calcium-dependent potassium channel and carried by a regenerative calcium current. This cellular dysfunction is thought to be present in all cell types in genetically hypertensive individuals, and a general framework is provided which tentatively explains the development, establishment and complex phenotype of essential hypertension.

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