Calcium signalling and imagining in smooth muscle of the urinogenital tract.

University of Glasgow (2004) J Physiol 557P, SA17

Research Symposium: Calcium signalling and imagining in smooth muscle of the urinogenital tract.

S. wray and T.V. Burdyga

Department of Physiology, The University of Liverpool, Liverpool, UK

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While it is clear that both local and global Ca signals contribute to excitability and contraction in smooth muscles, the details of these mechanisms remain to be elucidated. It is however apparent that smooth muscle in different tissues may use different mechanisms to tailor its activity to each particular tissue. In this presentation we will compare and contrast two phasic smooth muscles of the urinogenital tract; uterus and ureter.It is important for the function of both these tissues that the muscular activity is phasic. In the ureter this allows for boluses of urine to pass from kidney to bladder, as urine is produced. In the uterus it allows for gradual expulsion of the fetus without hypoxic damage. From our studies it would appear that the mechanisms controlling this phasic activity are however very different. Both smooth muscles rely on action potentials being triggered to activate Ca entry and produce contraction. Both also have a substantial SR containing both IP3 and/or ryanodine receptors. In the intact uterus it has been shown that spontaneous activity does not depend upon the SR, and direct measurements of SR Ca in single cells have confirmed this. Imagining of uterine cells and intact strips reveal large global changes in Ca with spontaneous activity. However local SR release events and spontaneous transient outward currents (STOCs) are rarely seen. In contrast in guinea-pig ureter, in isolated cells and cells in situ, Ca sparks are readily seen. Ca sparks are generated by at least one frequent discharging site located close to the edge of the cell membrane several microns away from the nucleus. The temporal characteristics of Ca sparks are similar to those of STOCs. Ca sparks and STOCs are potentiated by low concentration of caffeine and inhibited by ryanodine and CPA. We will show that Ca sparks, by targeting BK channels, play an important role in control of the excitability of the guinea pig ureter, producing a refractory period of 20-40s. During the refractory period suprathreshold depolarising pulses produce regional Ca transient the amplitude of which is minimal at the beginning and maximal before the termination of the refractory period. The refractory period was eliminated by ryanodine, CPA or TEA. The data obtained suggest that in the guinea pig, Ca sparks are playing a key role in controlling the excitability of the ureteric muscle and protecting it from undergoing a tetanic contraction. This is in marked contrast to the uterine muscle, where the refractory period was not readily detected and an increase in the spike frequency resulted in stronger, prolonged contractions, suited to labour



Where applicable, experiments conform with Society ethical requirements.

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