The long term objective of this research is to characterize transmission through cat bladder parasympathetic ganglia and thereby to define the local neuronal interactions which may contribute to the integrative function of autonomic ganglia and to higher CNS functions involved in memory and learning. Information derived from this research would enhance our understanding of the neural control of the urinary bladder and its physiology and pharmacology. Local neuronal interactions which occur during ganglionic transmission will be analyzed in cat parasympathetic ganglia of the urinary bladder using intracellular, single and double electrode voltage clamp and single channel- patch clamp analysis. The local neuronal interactions which will be analyzed in this proposal are endogenously occurring synaptic events mediated by three different neurotransmitters, namely, acetylcholine (ACh), norepinephrine (NE) and adenosine. Evidence suggests that all three of these endogenous neurotransmitter mediated hyperpolarizing synaptic potentials are mediated by a calcium dependent potassium conductance. The outward K currents underlying the sow inhibitory synaptic potentials in cat bladder parasympathetic ganglia will be analyzed as well as pharmacological charcteristics of and possible second messenger systems underlying the synaptic responses mediated by the neurotransmitters, acetylcholine, norepinephrine, and adenosine. In addition the membrane K channels activated by ACh, NE, and adenosine wil be compared with the properties of Ca-activated K channels located in the membranes of cat bladder parasympathic neurons. The above studies should provide essential information about the membrane mechanisms involved in neuronal communication between pre- and post-synaptic neurons, and about possible mechanisms linking electrophysiological events with intracellular second messengers and cell metabolism. Analysis of the mechanisms underlying these local neuronal interactions may lead to a better understanding of autonomic function, as well as """"""""higher"""""""" brain functions involved in memory, learning, and behavior. In addition, the information obtained form pharmacological analysis of these synaptic mechanisms may eventually result in the use of drugs which are more clinically effective in the treatment of CNS disorders, as well as autonomic dysfunction, particularly, bladder dysfunction.
