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A cold‐ and menthol‐activated current in rat dorsal root ganglion neurones: properties and role in cold transduction
Author(s) -
Reid Gordon,
Babes Alexandru,
Pluteanu Florentina
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.024331
Subject(s) - trpm8 , thermoreceptor , dorsal root ganglion , biophysics , depolarization , menthol , chemistry , current clamp , transduction (biophysics) , extracellular , cold sensitivity , voltage clamp , receptor , membrane potential , biology , anatomy , biochemistry , transient receptor potential channel , trpv1 , dorsum , organic chemistry , mutant , gene
Skin temperature is sensed by peripheral thermoreceptors. Using the neuronal soma in primary culture as a model of the receptor terminal, we have investigated the mechanisms of cold transduction in thermoreceptive neurones from rat dorsal root ganglia. Cold‐sensitive neurones were pre‐selected by screening for an increase in [Ca 2+ ] i on cooling; 49 % of them were also excited by 0.5 μ m capsaicin. Action potentials and voltage‐gated currents of cold‐sensitive neurones were clearly distinct from those of cold‐insensitive neurones. All cold‐sensitive neurones expressed an inward current activated by cold and sensitised by (‐)‐menthol, which was absent from cold‐insensitive neurones. This current was carried mainly by Na + ions and caused a depolarisation on cooling accompanied by action potentials, inducing voltage‐gated Ca 2+ entry; a minor fraction of Ca 2+ entry was voltage‐independent. Application of (‐)‐menthol shifted the threshold temperatures of the cold‐induced depolarisation and the inward current to the same extent, indicating that the cold‐ and menthol‐activated current normally sets the threshold temperature for depolarisation during cooling. The action of menthol was stereospecific, with the (+)‐isomer being a less effective agonist than the (‐)‐isomer. Extracellular Ca 2+ modulated the cold‐ and menthol‐activated current in a similar way to its action on intact cold receptors: lowered [Ca 2+ ] o sensitised the current, while raised [Ca 2+ ] o antagonised the menthol‐induced sensitisation. During long cooling pulses the current showed adaptation, which depended on extracellular Ca 2+ and was mediated by a rise in [Ca 2+ ] i . This adaptation consisted of a shift in the temperature sensitivity of the channel. In capsaicin‐sensitive neurones, capsaicin application caused a profound depression of the cold‐activated current. Inclusion of nerve growth factor in the culture medium shifted the threshold of the cold‐activated current towards warmer temperatures. The current was blocked by 50 μ m capsazepine and 100 μ m SKF 96365. We conclude that the cold‐ and menthol‐activated current is the major mechanism responsible for cold‐induced depolarisation in DRG neurones, and largely accounts for the known transduction properties of intact cold receptors.