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

被引:79
作者
Piper, AS
Yeats, JC
Bevan, S
Docherty, RJ
机构
[1] Univ London Kings Coll, Guys Sch Med, Dept Pharmacol, London SE1 7EH, England
[2] Univ London Kings Coll, Kings Sch Med, Dept Pharmacol, London SE1 7EH, England
[3] Univ London Kings Coll, St Thomas Sch Med, Dept Pharmacol, London SE1 7EH, England
[4] Univ London Kings Coll, St Thomas Sch Dent & Biomed Sci, Dept Pharmacol, London SE1 7EH, England
[5] Univ London Kings Coll, Guys Sch Dent & Biomed Sci, Dept Pharmacol, London SE1 7EH, England
[6] Univ London Kings Coll, Kings Sch Dent & Biomed Sci, Dept Pharmacol, London SE1 7EH, England
[7] Novartis Inst Med Sci, London WC1 6BN, England
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1999年 / 518卷 / 03期
基金
英国惠康基金;
关键词
D O I
10.1111/j.1469-7793.1999.0721p.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 mu M) was significantly less when the holding potential (V-h) 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 mu M) 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.
引用
收藏
页码:721 / 733
页数:13
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