NEUROMUSCULAR TRANSMISSION IN URINARY SMOOTH MUSCLE

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A proposal is presented to establish a laboratory to study the cellular properties of neuromuscular transmission in the smooth muscle of the three major functional areas of the human lower urinary tract using intracellular microelectrodes, tension recording, and classical pharmacological intervention. Tissue will be obtained from adults and children with normal and abnormal urinary muscle function undergoing open urologic operations. Experiments will be designed to examine the mechanical and electrical responses of muscle strips to nerve stimulation and to identify the neurotransmitters responsible by reproducing and abolishing the response with selected agonists and antagonists. The contribution of adenosine 5'-triphosphate to non-adrenergic non-cholinergic transmission will be particularly examined because growing evidence supports the role of this compound in such transmission in several adrenergic and cholinergic systems. Changes in membrane excitability as manifested by changes in the resting membrane potential and the response to stimulation by agonists, depolarizing solutions and electrical stimulation will be examined in normal and abnormal urinary muscle because preliminary evidence suggests that such changes may be implicated in pathologically abnormal urinary muscle associated with clinical motility disorders. It is hoped that the work resulting from this proposal will contribute to existing knowledge of normal cellular events associated with voiding, will identify significant similarities and differences among the functional regions of the urinary tract, and will contribute toward understanding the extent to which changes in the cellular mechanisms of urinary tract smooth muscle contribute to clinical disorders of urinary tract motility. The applicant is a qualified clinical urologist with three years experience in the laboratory study of Smooth Muscle. This award would constitute a major opportunity for the applicant to develop his research and clinical goals, to establish an independent laboratory to investigate basic mechanism of urinary tract smooth muscle while continuing his clinical work with patients with neuromuscular bladder disorders.