Excitability of lower urinary tract smooth muscles: functional implications.

University of Oxford (2005) J Physiol 568P, SA24

Research Symposium: Excitability of lower urinary tract smooth muscles: functional implications.

Brading, Alison Frances;

1. Department of Pharmacology, University of Oxford, Oxford, United Kingdom.

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The three functionally important smooth muscles of the lower urinary tract (ureters, detrusor and urethral smooth muscle) normally show remarkably different patterns of activity. In ureters regular propagated action potentials originating from the renal pelvis trigger contractions propelling urine into the bladder. In the detrusor spontaneous action potentials arise in the muscle bundles but are not propagated far, allowing non-synchronized contractile activity that enables the bladder to sustain a compact shape during filling without significant rise in intravesical pressure, and the urethral smooth muscle maintains constant tone probably without developing action potentials, to prevent leakage of urine during filling. Although these activities were originally called myogenic, since they persists in the presence of tetrodotoxin, it is becoming apparent that in all three tissues this spontaneous activity is either initiated or modulated by another class of cells with features similar to the interstitial cells of Cajal seen in gastrointestinal smooth muscles (ICC-like cells). These cells are thought to regularly inject depolarizing current through gap junctions into their adjacent smooth muscle cells, activating a variety of voltage sensitive channels leading to the characteristic electrical and mechanical activity seen. The effects of activity in autonomic nerves to these three muscles also differ. Contractile activity cannot be initiated in the ureteric smooth muscles through autonomic motor nerves, although application of potential transmitters may modulate the action potential shape and resulting contraction. Detrusor smooth muscle is densely innervated by parasympathetic nerves, which can elicit action potentials and synchronized contraction of the detrusor to elevate bladder pressure. Urethral smooth muscles are innervated by multiple inhibitory and excitatory nerves that can suppress or enhance the contractile tone. Histological techniques suggest that both autonomic nerves and collaterals of sensory nerves may innervate both smooth muscle cells and ICC-like cells, and a variety of different receptors are present on both types of cell. Many different molecular pathways have been implicated in neural modulation of contractile activity, including those by-passing the membrane, but many types of ion channel are present in smooth muscles and ICC-like cells, and may represent molecular targets for the transmitters. This communication will discuss in particular the excitability of the detrusor muscle, since one of the most common disorders of the urinary system is bladder overactivity. In this condition increased spontaneous contractile activity may result in symptoms of urgency and elevation of bladder pressure, which may result in incontinence. Pharmacological control of this condition is not yet optimal, and considerable effort is being spent to develop drugs that can selectively reduce this activity. Increased understanding of the mechanisms involved in its generation is still necessary.



Where applicable, experiments conform with Society ethical requirements.

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