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

• Published in: The Journal of physiology Vol. 518; no. 3; pp. 721 - 733
• Main Authors: Piper, A. S., Yeats, J. C., Bevan, S., Docherty, R. J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 01.08.1999; Blackwell Science Ltd; Blackwell Science Inc
• Subjects: Animals; Calcineurin - pharmacology; Calcineurin Inhibitors; Calcium - physiology; Calcium Signaling - drug effects; Calcium Signaling - physiology; Capsaicin - pharmacology; Chelating Agents - pharmacology; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Electric Stimulation; Electrophysiology; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Ion Channels - drug effects; Ion Channels - physiology; Magnesium - physiology; Male; Membrane Potentials - physiology; Microdialysis; Neurons, Afferent - drug effects; Original; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Rats, Wistar
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.1999.0721p.x

Responses to capsaicin in isolated sensory neurones have been shown to desensitize in a Ca 2+ - 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 ( V h ) was +40 mV rather than -60 mV. This was not due only to reduced Ca 2+ 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 Ca 2+ chelator BAPTA. Addition of a pseudosubstrate inhibitor of the Ca 2+ -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 Ca 2+ or Mg 2+ did not reverse the increase in outward rectification of capsaicin-activated current after Ca 2+ -dependent desensitization had occurred. This indicates that a voltage-dependent block of the capsaicin-activated ion channel by Ca 2+ or Mg 2+ was not responsible for the observed changes in the properties of the capsaicin-activated conductance.