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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS016228-09
Application #
3396758
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1980-04-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1991-03-31
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
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Kumamoto, E; Nohmi, M; Shinnick-Gallagher, P (1989) Fast hyperpolarization following an excitatory postsynaptic potential in cat bladder parasympathetic neurons. Neuroscience 30:671-81
Kumamoto, E; Shinnick-Gallagher, P (1987) Postganglionic stimulation activates synaptic potentials in cat bladder parasympathetic neurons. Brain Res 435:403-7
Akasu, T; Gallagher, J P; Hirai, K et al. (1986) Vasoactive intestinal polypeptide depolarizations in cat bladder parasympathetic ganglia. J Physiol 374:457-73
Akasu, T; Shinnick-Gallagher, P; Gallagher, J P (1986) Evidence for a catecholamine-mediated slow hyperpolarizing synaptic response in parasympathetic ganglia. Brain Res 365:365-8
Nohmi, M; Shinnick-Gallagher, P; Gallagher, J P (1986) Characterization of gamma-aminobutyric acid responses with sulfate loading in cat bladder neurons. Neurosci Lett 69:182-7
Nohmi, M; Shinnick-Gallagher, P; Gean, P W et al. (1986) Calcitonin and calcitonin gene-related peptide enhance calcium-dependent potentials. Brain Res 367:346-50