Nociceptors lacking TRPV1 and TRPV2 have normal heat responses.
Vanilloid receptor 1 (TRPV1) has been proposed to be the principal heat-responsive channel for nociceptive neurons. The skin of both rat and mouse receives major projections from primary sensory afferents that bind the plant lectin isolectin B4 (IB4). The majority of IB4-positive neurons are known to be heat-responsive nociceptors. Previous studies suggested that, unlike rat, mouse IB4-positive cutaneous afferents did not express TRPV1 immunoreactivity. Here, multiple antisera were used to confirm that mouse and rat have different distributions of TRPV1 and that TRPV1 immunoreactivity is absent in heat-sensitive nociceptors. Intracellular recording in TRPV1(-/-) mice was then used to confirm that TRPV1 was not required for detecting noxious heat. TRPV1(-/-) mice had more heat-sensitive neurons, and these neurons had normal temperature thresholds and response properties. Moreover, in TRPV1(-/-) mice, 82% of heat-responsive neurons did not express immunoreactivity for TRPV2, another putative noxious heat channel.
Woodbury
C Jeffery
CJ
Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Zwick
Melissa
M
Wang
Shuying
S
Lawson
Jeffrey J
JJ
Caterina
Michael J
MJ
Koltzenburg
Martin
M
Albers
Kathryn M
KM
Koerber
H Richard
HR
Davis
Brian M
BM
D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D004817:Epidermis / Q000502:physiology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology*; D006358:Hot Temperature; D007473:Ion Channels / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000737:chemistry* / Q000502:physiology; D009619:Nociceptors / Q000737:chemistry / Q000502:physiology*; D037121:Plant Lectins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D013045:Species Specificity; D050916:TRPV Cation Channels
D015220:Calcium Channels; D007473:Ion Channels; D037121:Plant Lectins; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C493922:Trpv1 protein, rat; C485717:Trpv2 protein, mouse; C476722:Trpv2 protein, rat