Abstract
Interstitial cells of Cajal-like cells (ICC-LCs) in the urethra may act as electrical pacemakers of spontaneous contractions. However, their properties in situ and their interaction with neighbouring urethral smooth muscle cells (USMCs) remain to be elucidated. To further explore the physiological role of ICC-LCs, spontaneous changes in [Ca(2+)](i) (Ca(2+) transients) were visualized in fluo-4 loaded preparations of rabbit urethral smooth muscle. ICC-LCs were sparsely distributed, rather than forming an extensive network. Ca(2+) transients in ICC-LCs had a lower frequency and a longer half-width than those of USMCs. ICC-LCs often exhibited Ca(2+) transients synchronously with each other, but did not often show a close temporal relationship with Ca(2+) transients in USMCs. Nicardipine (1 microm) suppressed Ca(2+) transients in USMCs but not in ICC-LCs. Ca(2+) transients in ICC-LCs were abolished by cyclopiazonic acid (10 microm), ryanodine (50 microm) and caffeine (10 mm) or by removing extracellular Ca(2+), and inhibited by 2-aminoethoxydiphenyl borate (50 microm) and 3-morpholino-sydnonimine (SIN-1; 10 microm), but facilitated by increasing extracellular Ca(2+) or phenylephrine (1-10 microm). These results indicated that Ca(2+) transients in urethral ICC-LCs in situ rely on both Ca(2+) release from intracellular Ca(2+) stores and Ca(2+) influx through non-L-type Ca(2+) channel pathways. ICC-LCs may not act as a coordinated pacemaker electrical network as do ICC in the gastrointestinal (GI) tract. Rather they may randomly increase excitability of USMCs to maintain the tone of urethral smooth muscles.