EFFECT OF DIFFERENT CALCIUM-CHANNEL BLOCKERS ON INHIBITORY JUNCTION POTENTIALS AND SLOW WAVES IN PORCINE ILEUM

The effect of several calcium channel blockers was evaluated: (i) on s pontaneous electrical and mechanical activities and (ii) on the respon se to electrical field stimulation. The study was carried out on whole -thickness preparation of porcine ileum. Glass microelectrodes were us ed to record membrane potential from smooth muscle cells. Resting memb rane potential was -60+/-2mV (n=18) and preparations generated spontan eous slow waves. Electrical field stimulation (EFS) was applied using different parameters. The amplitude and duration of inhibitory junctio n potentials (IJPs) increased with EFS strength. IJPs were abolished b y tetrodotoxin (1 mu M). Nifedipine (1 mu M) did not modify the amplit ude or duration of IJPs. The frequency of slow waves was not modified, however a slight but significant (p<0.001) reduction in slow wave dur ation was observed. Mechanical activity was abolished in presence of n ifedipine within approximately 6 min. omega-agatoxin IVA (50 nM) or om ega-conotoxin MVIIC (100 nn), respectively a P-type and a Q-type calci um channel blockers, did not modify slow wave and IJP characteristics. In contrast, in presence of omega-conotoxin GVIA (100 nM), a N-type c alcium channel blocker, or omega-conotoxin MWC (1 mu M), IJPs were com pletely abolished. These data suggest that, in porcine ileum, N-type b ut not P-,Q- or L-type calcium channels are involved in the release of the non-adrenergic noncholinergic neurotransmitters mediating IJPs. L -type calcium channels underlie electrical mechanical coupling but are not involved in slow wave generation.