Lack of potentiating effect of increasing temperature on responses to chemical activators in vagal sensory neurons isolated from TRPV1-null mice.
Our recent study (Ni D, Lee LY. Am J Physiol Lung Cell Mol Physiol 294: L563-L571, 2008) demonstrated that the responses of rat pulmonary sensory neurons to transient receptor potential vanilloid (TRPV)1 activators were enhanced by increasing temperature, but the role of the TPRV1 channel in this potentiating effect could not be definitively evaluated. In the present study, we used whole cell perforated patch-clamp technique to compare the responses of isolated nodose/jugular sensory neurons to chemical activators and increasing temperature between wild-type (WT) and TRPV1-null (TRPV1-/-) mice. Our results showed that, in voltage-clamp mode, the peak inward current evoked by hyperthermia was not different between WT and TRPV1-/- neurons; however, the inward current evoked by 2-aminoethoxydiphenyl borate (2-APB), a common activator of TRPV1-3 channels, was greatly potentiated by increasing temperature from 36 to 40.5 degrees C in WT neurons (n = 9; P < 0.01) but was not affected by the same change in temperature in TRPV1-/- neurons (n = 9; P = 0.54). Similarly, the inward current evoked by acid (pH 5.5), an activator of both TRPV1 channel and the acid-sensing ion channel, was enhanced by increasing temperature (n = 7; P < 0.05) in WT neurons, and this potentiating effect was absent in TRPV1-/- neurons (n = 13; P = 0.11). These results demonstrated that deletion of the TRPV1 channel does not significantly alter the stimulatory effect of hyperthermia on nodose/jugular neurons but eliminates the potentiating effect of increasing temperature on the responses of these neurons to nonselective TRPV1 channel activators. This study further suggests that a positive interaction between these chemical activators and increasing temperature at the TRPV1 channel is primarily responsible for the hyperthermia-induced sensitization of these neurons.
Ni
Dan
D
Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
Lee
Lu-Yuan
LY