Effect of different calcium channel blockers on inhibitory junction potentials and slow waves in porcine ileum

Abstract

The effect of several calcium channel blockers was evaluated: (i) on spontaneous electrical and mechanical activities and (ii) on the response to electrical field stimulation. The study was carried out on whole-thickness preparation of porcine ileum. Glass microelectrodes were used to record membrane potential from smooth muscle cells. Resting membrane potential was -60 +/- 2mV (n = 18) and preparations generated spontaneous slow waves. Electrical field stimulation (EFS) was applied using different parameters. The amplitude and duration of inhibitory junction potentials (IJPs) increased with EFS strength. IJPs were abolished by tetrodotoxin (1 microM). Nifedipine (1 microM) did not modify the amplitude or duration of IJPs. The frequency of slow waves was not modified, however a slight but significant (p < 0.001) reduction in slow wave duration was observed. Mechanical activity was abolished in presence of nifedipine within approximately 6 min. omega-agatoxin IVA (50 nM) or omega-conotoxin MVIIC (100 nM), respectively a P-type and a Q-type calcium channel blockers, did not modify slow wave and IJP characteristics. In contrast, in presence of omega-conotoxin GVIA (100 nM), a N-type calcium channel blocker, or omega-conotoxin MVIIC (1 microM), IJPs were completely abolished. These data suggest that, in porcine ileum, N-type but not P-,Q- or L-type calcium channels are involved in the release of the non-adrenergic non-cholinergic neurotransmitters mediating IJPs. L-type calcium channels underlie electrical mechanical coupling but are not involved in slow wave generation.