Spontaneous rhythmic inward currents recorded in interstitial cells of rabbit portal vein

It is now well established that smooth muscle of the portal vein exhibits spontaneous rhythmic contraction in vitro. The present study was designed to investigate the pacemaking mechanism(s) underlying the spontaneous rhythmic contractions in the rabbit portal vein (RPV). Using whole-cell patch clamp techniques, spontaneous inward currents were recorded at -60 mV of holding potential in freshly dispersed c-Kit immunopositive interstitial cells (ICs) isolated from sections of RPV. The inward currents were abolished by caffeine, FCCP, thapsigargin, and ryanodine, but were partially inhibited by 2-APB. Both gadolinium, a non-selective cation channel inhibitor, and niflumic acid, a chloride channel blocker, inhibited the inward currents completely. Replacement of external Na(+) with NMDG(+) also blocked the inward currents. W-7, a calmodulin inhibitor, increased both the amplitude and frequency of the inward currents. Taken together, these results indicate that non-selective cationic channels are involved in the generation of spontaneous inward currents recorded from ICs. Intracellular calcium concentration and calmodulin regulate the spontaneous inward currents, which may account for spontaneous rhythmic contraction in the RPV, but a role of chloride channels may not be excluded in the present study.