TRPV3 and TRPV4 Ion Channels are Not Major Contributors to Mouse Heat Sensation

Abstract

BackgroundThe discovery of heat-sensitive Transient Receptor Potential Vanilloid (TRPV) ion channels provided a potential molecular explanation for the perception of innocuous and noxious heat stimuli. TRPV1 has a significant role in acute heat nociception and inflammatory heat hyperalgesia. Yet, substantial innocuous and noxious heat sensitivity remains in TRPV1 knockout animals. Here we investigated the role of two related channels, TRPV3 and TRPV4, in these capacities. We studied TRPV3 knockout animals on both C57BL6 and 129S6 backgrounds, as well as animals deficient in both TRPV3 and TRPV4 on a C57BL6 background. Additionally, we assessed the contributions of TRPV3 and TRPV4 to acute heat nociception and inflammatory heat hyperalgesia during inhibition of TRPV1.ResultsTRPV3 knockout mice on the C57BL6 background exhibited no obvious alterations in thermal preference behavior. On the 129S6 background, absence of TRPV3 resulted in a more restrictive range of occupancy centered around cooler floor temperatures. TRPV3 knockout mice showed no deficits in acute heat nociception on either background. Mice deficient in both TRPV3 and TRPV4 on a C57BL6 background showed thermal preference behavior similar to wild-type controls on the thermal gradient, and little or no change in acute heat nociception or inflammatory heat hyperalgesia. Masking of TRPV1 by the TRPV1 antagonist JNJ-17203212 did not reveal differences between C57BL6 animals deficient in TRPV3 and TRPV4, compared to their wild-type counterparts.ConclusionsOur results support the notion that TRPV3 and TRPV4 likely make limited and strain-dependent contributions to innocuous warm temperature perception or noxious heat sensation, even when TRPV1 is masked. These findings imply the existence of other significant mechanisms for heat perception.