Differential effects of temperature on acid-activated currents mediated by TRPV1 and ASIC channels in rat dorsal root ganglion neurons.
Elevated temperature and decreased extracellular pH are hallmarks of inflammatory pain states. Dorsal root ganglia (DRG) neurons are integral in transferring painful stimuli from the periphery to central sites. This study investigated the effect of elevated temperatures on the response of DRG neurons to acute application of acidic solutions. At room temperature (22 degrees C), in response to pH 5.5, there were a variety of kinetic responses consistent with differential expression of TRPV1 and ASIC channels. Increasing the temperature resulted in a significant increase in the peak and total current mediated by TRPV1 in response to an acidic solution. In contrast, the amplitude of a fast activating, rapidly inactivating ASIC1-like current was not affected by increasing the temperature but did result in an increased rate of desensitization that reduced the total current level. This effect on the rate of desensitization was temperature-dependent and could be reversed by returning to 22 degrees C. Likewise, cells exhibiting slowly inactivating ASIC2-like responses also had temperature-dependent increase in the rate of desensitization. The ASIC2-like responses and the TRPV1 responses tended to decrease in amplitude with repetitive application of pH 5.5 even at 22 degrees C. The rate of desensitization of ASIC-like currents activated by less acidic solutions (pH 6.8) was also increased in a temperature-dependent manner. Finally, acidic pH reduced threshold to trigger action potentials, however, the pattern of action potential firing was shaped by the distribution of ASIC and TRPV1 channels. These results indicate that the ambient temperature at which acidosis occurs has a profound effect on the contribution of ASIC and TRPV1 channels, therefore, altering the neuronal excitability.
Neelands
Torben R
TR
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R4PM, AP9A, Abbott Park, IL 60064-6123, USA. Torben.Neelands@Abbott.com
Zhang
Xu-Feng
XF
McDonald
Heath
H
Puttfarcken
Pamela
P
D062565:Acid Sensing Ion Channels; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology*; D006863:Hydrogen-Ion Concentration; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*; D013696:Temperature
D062565:Acid Sensing Ion Channels; C568268:Asic1 protein, rat; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat