Search

Gap junctions (GJ) connect the cytoplasm of two adjacent cells and have two probable functions, synchronisation of networks by direct electrical communication and allowing. the passage of small molecules. This thesis examines the distribution patterns and physiological roles of the neuronal GJ sub unit connexin 36 (Cx36) in autonomic and respiratory control. Using the working heart brainstem preparation of the rat and mouse recordings were made during baseline and during peripheral chemoreceptor and baroreceptor stimulation. Central sympathetic drive was attenuated with the addition of 1 μM of mefloquine (M F) to the perfusate. MF (which blocks Cx36 containing GJs) induced a resting bradycardia, attenuated the amplitude of respiratory related sympathetic bursts, attenuated chemoreceptor-induced sympathoexcitation and increased heart rate recovery time after chemoreceptor stimulation. Attenuated respiratory responses to autonomic reflex stimulation were observed with MF, no significant alterations in baroreflex sensitivity were observed. Studies in Cx36 knockout mice were analogous to data obtained with MF. Telemetric probes inserted in free running wild type and Cx36 knockout mice which continually recorded heart rate and arterial pressure revealed significantly augmented variations in resting heart rate and arterial pressure in Cx36 knockout mice in comparison to wild type mice. Autonomic reflexes examined in anaesthetised Cx36 knockout mice revealed attenuated heart rate changes in response to chemoreceptor stimulation. Cx36 immunoreactivity and Cx36 cyan fluorescent protein expression was reported at various brainstem and spinal cord sites involved in autonomic function including, the nucleus of the solitary tract and sympathetic preganglionic neurones (SPNs). The results revealed that Cx36, at the level of the SPNs, plays important roles in regulating sympathetic outflow. This may have important clinical implications as an imbalance in the sympathetic and parasympathetic outflow to the heart for example, underlies various maladies from hypertension to cardiac arrhythmias