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1 Responses to capsaicin in isolated sensory neurones have been shown to desensitize in a Ca2+‐ and voltage‐dependent manner. We have studied desensitization of capsaicin‐activated currents in cultured adult rat dorsal root ganglion (DRG) neurones over a range of membrane potentials using whole‐cell patch‐clamp techniques. 2 Acute desensitization of responses to capsaicin (0.5 μM) was significantly less when the holding potential (Vh) was +40 mV rather than ‐60 mV. This was not due only to reduced Ca2+ entry as the response to capsaicin was desensitized by the same amount whether prior exposure to capsaicin was at ‐60 or +40 mV. The I‐V relationship for capsaicin‐induced current, determined using a voltage step protocol, was outwardly rectifying and during the acute phase of desensitization the degree of outward rectification increased. 3 Acute desensitization and the increase in outward rectification that accompanied desensitization were inhibited when cells were dialysed with the rapid Ca2+ chelator BAPTA. Addition of a pseudosubstrate inhibitor of the Ca2+‐calmodulin‐dependent enzyme calcineurin (CI, 100 μM) prevented the increase in outward rectification although it did not cause a significant decrease of acute desensitization. 4 Removal of external Ca2+ or Mg2+ did not reverse the increase in outward rectification of capsaicin‐activated current after Ca2+‐dependent desensitization had occurred. This indicates that a voltage‐dependent block of the capsaicin‐activated ion channel by Ca2+ or Mg2+ was not responsible for the observed changes in the properties of the capsaicin‐activated conductance.
The Journal of Physiology – Wiley
Published: Aug 1, 1999
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