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The effect of capsaicin on voltage‐gated calcium currents and calcium signals in cultured dorsal root ganglion cells
Author(s) -
Bleakman D.,
Brorson J.R.,
Miller R.J.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12725.x
Subject(s) - capsaicin , ruthenium red , chemistry , dorsal root ganglion , egta , bapta , biophysics , depolarization , calcium , patch clamp , membrane potential , tetrodotoxin , voltage clamp , electrophysiology , medicine , endocrinology , anatomy , dorsum , biochemistry , biology , receptor , organic chemistry
1 The effects of capsaicin on voltage‐gated Ca 2+ currents (I Ca ), and intracellular Ca 2+ concentrations ([Ca 2+ ] i ) in cultured dorsal root ganglion (DRG) neurones of the rat were examined in vitro by use of combined patch clamp‐microfluorometric recordings. 2 Under voltage‐clamp conditions, capsaicin (0.1–10 μ m ) caused a concentration‐dependent decrease in the magnitude of the I Ca , an elevation in the holding current (I h ) and a concomitant rise in the [Ca 2+ ] i in most cells examined. Repeated application of capsaicin produced marked desensitization. 3 Some decrease in the I Ca produced by capsaicin was also observed when the rise in [Ca 2+ ] i was buffered with EGTA or BAPTA and when Ba 2+ was used as the charge carrier; under these conditions the desensitization previously observed was smaller. 4 The decrement in voltage‐gated current was smaller in Ba 2+ containing solutions than in Ca 2+ containing solutions suggesting that the capsaicin‐induced influx of Ca 2+ partially mediated the observed decrease in the voltage‐gated current. In cells which showed a marked response to capsaicin an outward (positive) current was sometimes observed upon depolarization from −80 to 0mV. This effect was consistent with an outward movement of cations through the capsaicin conductance pathway which may also account, in part, for the apparent reduction in I Ca by capsaicin. 5 The effects of capsaicin under voltage‐clamp conditions were prevented by ruthenium red (1 μ m ). 6 Under current clamp conditions, capsaicin depolarized and caused a rise in [Ca 2+ ] i in the majority of DRG cells examined. Both of these effects could be prevented by ruthenium red (500 n m ). 7 It is concluded that capsaicin reduces the I Ca of rat DRG neurones primarily by indirect mechanisms.