By using all available electrophysiological techniques, including tight-seal patch-clamp methods, we will attempt to secure the basic information concerning the characteristics of the ionic channels in the smooth muscles of the normal urinary tract. This will be a multilevel study, ranging from tissue phenomena, through individual dispersed cells to single-channel events. We believe that such fundamental knowledge serves as an essential basis for understanding pathophysiological derangements in disease states. The properties to be learned include the nature of the charge-carriers, kinetics of activation, inactivation, deactivation, and reactivation of various conductances, reversal potentials, and pharmacological responses. Differences in the properties of ionic channels in different parts of the urinary tract will be examined to provide a basis of understanding the varied functions of the different parts. Also species differences will be explored in search for the optimum animal model for human urinary tract tissues. The actions of cholinergic, adrenergic, purinergic, and peptide neurotransmitters, as well as those of calcium-channel effectors will be studied at all the levels of cellular organization mentioned.
A specific aim i s to obtain information applicable to clinical therapeutic uses.
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