The Effect of Sex on GABAA Receptor Activation on Vasopressin Neurons from the Supraoptic Nucleus

Arginine Vasopressin (AVP), a hormone produced by the magnocellular neurosecretory cells (MNC) of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus regulates fluid balance and plasma osmolality in healthy individuals. During congestive heart failure (CHF) and liver failure, however, AVP becomes dysregulated leading to increased renal water reabsorption and consequently persistent hyponatremia. Previous work done in the laboratory suggests that female rats may be protected from such dysregulation, perhaps by hormones such as estrogen. Our hypothesis is that under normal physiological conditions, activation of the GABAA receptor inhibits vasopressin neurons within the SON by causing chloride influx, but that under pathophyisiological conditions, activation of the GABAA receptor induces chloride efflux thereby causing activation of the vasopressin neurons in males. It is not known if AVP neurons from female rats behave in a similar manner to AVP neurons from males or are influenced by the estrous cycle. To test our hypothesis, the SON of adult, intact Sprague Dawley rats of both sexes were bilaterally injected with the ClophensorN virus which is a genetically modified virus used to detect Chloride flux in vasopressin neurons using fluorescence. Dissociated neurons from the SON were tested to assess chloride flux in response to the GABAA receptor agonist muscimol. Results show that under normal physiological conditions, muscimol induces Chloride influx in both males and females. Future experiments will assess the effect of GABAA activation in pathophysiological conditions by using the bile-duct ligation model of liver failure.