Cajal beyond the gut: interstitial cells in the urinary system - towards general regulatory mechanisms of smooth muscle contractility ?

Interstitial cells of Cajal (ICC), similar to GI pacemakers have been identified throughout the urinary system. Although each part of the system serves a different function, ranging from peristalsis of the ureters, storage of urine by the bladder, and a sphincteric action by the urethra, they share a common mechanism in being able to generate phasic myogenic contractions. Even the urethra, often considered to be a 'tonic' smooth muscle, achieves an apparently sustained contraction by averaging numerous small asynchronous 'phasic' contractions. This activity can occur in the absence of any neural input, implying the presence of an intrinsic pacemaker. Intracellular microelectrode recordings from urethral muscle strips reveal electrical slow waves similar to those of the GI tract. To study this further, we isolated single cells from rabbit urethra and found not only smooth muscle cells (SMC), but a second cell type comprising -10% of the total. The latter cells were branched and non-contractile and closely resembled intestinal ICC. Electrophyiological studies revealed that, while the isolated smooth muscle cells were electrically quiescent, the 'ICC' fired electrical slow waves similar to those observed in the whole tissue. The basis of this difference was the presence of a large pacemaker current involving the activation of calcium-activated Cl channels by spontaneous intracellular Ca2+ waves. These, in turn, have been shown to be modulated by neurotransmitters such as nitric oxide, noradrenaline and ATP, thus providing a possible mechanism whereby neural regulation of the urethra, as well as spontaneous tone, may be mediated via ICC.