A study of the voltage dependence of capsaicin-activated membrane currentsin rat sensory neurones before and after acute desensitization

1. Responses to capsaicin in isolated sensory neurones have been shown to d esensitize in a Ca2+- and voltage-dependent manner. We have studied desensi tization of capsaicin-activated currents in cultured adult rat dorsal root ganglion (DRG) neurones over a range of membrane potentials using whole-cel l patch-clamp techniques. 2. Acute desensitization of responses to capsaicin (0.5 mu M) was significa ntly less when the holding potential (V-h) was +40 mV rather than -60 mV. T his 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, determi ned using a voltage step protocol, was outwardly rectifying and during the acute phase of desensitization the degree of outward rectification increase d. 3. Acute desensitization and the increase in outward rectification that acc ompanied desensitization were inhibited when cells were dialysed with the r apid Ca2+ chelator BAPTA. Addition of a pseudosubstrate inhibitor of the Ca 2+-calmodulin-dependent enzyme calcineurin (CI, 100 mu M) prevented the inc rease in outward rectification although it did not cause a significant decr ease 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 desensit ization 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.