Two Ca2+ entry pathways mediate InsP3-sensitive store refilling in guinea-pig colonic smooth muscle

1. Sarcolemma Ca2+ influx, necessary for store refilling, was well maintained, over a wide range (-70 to + 40 mV) Of membrane voltages, in guinea-pig single circular colonic smooth muscle cells, as indicated Ly the magnitude of InsP(3)-evoked Ca2+ transients. 2. This apparent voltage independence of store refilling was achieved by the activity of sarcolemma Ca2+ channels some of which were voltage gated while others were not. At negative membrane potentials (e.g. -70 mV), Ca2+ influx through channels which lacked voltage gating provided for store refilling while at positive membrane potentials (e.g. +40 mV) voltage-gated Ca2+ channels were largely responsible. 3. Sarcolemma voltage-gated Ca2+ currents were not activated following store depletion. 4. Removal of external Ca2+ or the addition of the Ca2+ channel blocker nimodipine (1 mu M) inhibited store refilling, as assessed by the magnitude of InsP(3)-evoked Ca2+ transients, with little or no change in bulk average cytoplasmic Ca2+ concentration. One hypothesis for these results is that the store may refill from a high subsarcolemma Ca2+ gradient. 5. Influx via channels, some of which are voltage gated and others which lack voltage gating, may permit the establishment of a subsarcolemma Ca2+ gradient. Store access to the gradient allows InsP(3)-evoked Ca2+ signalling to be maintained over a wide voltage range in colonic smooth muscle.