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Ca 2+ influx through voltage‐gated Ca 2+ channels regulates 5‐HT 3 receptor channel desensitization in rat glioma × mouse neuroblastoma hybrid NG108–15 cells
Author(s) -
Jones Susan,
Yakel Jerrel L.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.361bk.x
Subject(s) - bapta , desensitization (medicine) , chemistry , biophysics , depolarization , membrane potential , egta , kinetics , calcium , receptor , biochemistry , biology , organic chemistry , physics , quantum mechanics
1 The kinetics of desensitization of the 5‐HT 3 receptor (5‐HT 3 R)‐gated ion channel were investigated using whole‐cell and perforated‐patch recording techniques in NG108–15 cells. 2 Rapid application of 5‐HT (50 μM) elicited a 5‐HT 3 R‐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 (Ca 2+ i ) with 5 mM EGTA (0.5 mM added Ca 2+ ; with an estimated free [Ca 2+ ] 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 %. 3 This slowing in the rate of desensitization was reduced by stronger Ca 2+ buffering (20 mM BAPTA, without added Ca 2+ ), or by the bath application of cadmium (100 μM) to block voltage‐gated Ca 2+ channels. The rate of desensitization was also dependent on membrane potential. 4 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. 5 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. 6 These data suggest that Ca 2+ influx through a cadmium‐sensitive voltage‐gated Ca 2+ channel increases the cytoplasmic Ca 2+ concentration ([Ca 2+ ] i ) and induces a dramatic slowing in the kinetics of desensitization of the 5‐HT 3 R channel. These data provide evidence for cross‐talk between voltage‐gated Ca 2+ channels and 5‐HT 3 Rs in NG108–15 cells.