Ca2+ influx through voltage‐gated Ca2+ channels regulates 5‐HT3 receptor channel desensitization in rat glioma × mouse neuroblastoma hybrid NG108–15 cells

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Abstract
The kinetics of desensitization of the 5‐HT3 receptor (5‐HT3R)‐gated ion channel were investigated using whole‐cell and perforated‐patch recording techniques in NG108–15 cells. Rapid application of 5‐HT (50 μM) elicited a 5‐HT3R‐mediated inward current response that desensitized completely in the continued presence of agonist. In the whole‐cell recording configuration (holding potential of −70 mV) while buffering internal calcium (Ca2+i) with 5 mM EGTA (0.5 mM added Ca2+; with an estimated free [Ca2+] of 30 nM), the rate of desensitization was initially rapid (with a half‐time of ≈230 ms), but dramatically slowed with time by 1120 ± 160 %. This slowing in the rate of desensitization was reduced by stronger Ca2+ buffering (20 mM BAPTA, without added Ca2+), or by the bath application of cadmium (100 μM) to block voltage‐gated Ca2+ channels. The rate of desensitization was also dependent on membrane potential. In perforated‐patch recordings, the rate of desensitization remained constant. However, a slowing in the desensitization rate could be induced by depolarizing cells immediately prior to the application of 5‐HT. The depolarization‐induced slowing was blocked by incubating cells with BAPTA‐AM (a membrane‐permeant analogue of BAPTA) or by the bath application of cadmium. These data suggest that Ca2+ influx through a cadmium‐sensitive voltage‐gated Ca2+ channel increases the cytoplasmic Ca2+ concentration ([Ca2+]i) and induces a dramatic slowing in the kinetics of desensitization of the 5‐HT3R channel. These data provide evidence for cross‐talk between voltage‐gated Ca2+ channels and 5‐HT3Rs in NG108–15 cells.

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