Thermosensitive channels open at hot or cold temperatures and mediate our perception of environmental temperature. Some of these channels also mediate non-thermally induced sensations of pain. These thermosensitive channels are expressed by cells of somatosensory ganglia as well as by cells of the skin. We have discovered a novel thermally gated channel activated by warming from painfully cold temperatures. This channel is activated by pain-relieving rather than pain-causing thermal stimulation. We find this thermally-induced current in a skin cell line. We also find that the gene encoding this channel is expressed by cells of the skin and perhaps also of the somatosensory ganglia that innervate the skin. We propose to determine by patch clamp recordings what temperature changes open and close this channel, what drugs block or fail to block it, and what ions pass through it. We intend to find out by in situ hybridization and antibody detection methods which cells express this channel's gene and protein, and will use calcium imaging or electrophysiological methods to determine whether these cells functionally express the resulting thermosensitive channel. Finally, we will determine the effects of knocking out the Trpml3 gene, focusing on the physiological response of cells and whole animals to temperature and other sensory stimuli. These studies aim to elucidate how we detect environmental temperature changes but also how antinociceptive or pleasurable sensation may take place.
Project Currently known thermosensitive channels do not account for all thermal stimuli we perceive. Furthermore, there is presently no knowledge of how pleasurable or pain- relieving stimuli may be detected other than by decreased activation of nociceptive receptors. The activation of TRPML3 channels by temperature changes when warming from painful cold may contribute to the understanding of both thermal sensation and pain relief.
|Lorenzen, Sarah M; Duggan, Anne; Osipovich, Anna B et al. (2015) Insm1 promotes neurogenic proliferation in delaminated otic progenitors. Mech Dev 138 Pt 3:233-45|
|Flores, Emma N; Duggan, Anne; Madathany, Thomas et al. (2015) A non-canonical pathway from cochlea to brain signals tissue-damaging noise. Curr Biol 25:606-12|
|García-Añoveros, Jaime; Wiwatpanit, Teerawat (2014) TRPML2 and mucolipin evolution. Handb Exp Pharmacol 222:647-58|
|Remis, Natalie N; Wiwatpanit, Teerawat; Castiglioni, Andrew J et al. (2014) Mucolipin co-deficiency causes accelerated endolysosomal vacuolation of enterocytes and failure-to-thrive from birth to weaning. PLoS Genet 10:e1004833|
|Flores, Emma N; García-Añoveros, Jaime (2011) TRPML2 and the evolution of mucolipins. Adv Exp Med Biol 704:221-8|
|Castiglioni, Andrew J; Remis, Natalie N; Flores, Emma N et al. (2011) Expression and vesicular localization of mouse Trpml3 in stria vascularis, hair cells, and vomeronasal and olfactory receptor neurons. J Comp Neurol 519:1095-1114|
|Rosenbaum, Jason N; Duggan, Anne; García-Añoveros, Jaime (2011) Insm1 promotes the transition of olfactory progenitors from apical and proliferative to basal, terminally dividing and neuronogenic. Neural Dev 6:6|
|Zheng, Lili; Zheng, Jing; Whitlon, Donna S et al. (2010) Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model. J Neurosci 30:7187-201|
|Tannous, Bakhos A; Christensen, Adam P; Pike, Lisa et al. (2009) Mutant sodium channel for tumor therapy. Mol Ther 17:810-9|
|Cornell, Robert A; Aarts, Michelle; Bautista, Diana et al. (2008) A double TRPtych: six views of transient receptor potential channels in disease and health. J Neurosci 28:11778-84|
Showing the most recent 10 out of 14 publications