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

摘要

class="enumerated" style="list-style-type:decimal">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.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.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.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.