1 1 Symposium Chemosensory Receptors Satellite DEVELOPMENT ...

157 Slide Taste ChemoreceptionHTAS2R38 HAPLOTYPES DETERMINE BITTERNESSRATINGS OF GLUCOSINOLATE CONTAININGVEGETABLESHakala M. 1 , Alarcon S.M. 1 , Estrella N. 1 , Breslin P.A. 1 1 MonellChemical Senses Center, Philadelphia, PAOur previous psychogenomic studies show that variations in humanTAS2R38 receptor haplotypes determine individual differences inbitterness perception of compounds that contain a thiourea (N-C=S)moiety, such as PTC and PROP (Bufe et al, 2005 Current Biology 22:322-327). Structurally related chemicals are contained within allglucosinolate generating vegetables, such as mustard greens, kale, andbrussel sprouts. The aim of this sensory study was to investigate theeffect of subjects´ TAS2R38 haplotype on the bitterness ratings oftwenty eight commercially available vegetables and plant products,which were presented randomly and in triplicate over three sessions.Trained subjects (n = 36) were screened for having TAS2R38haplotypes of: PAV/PAV (sensitive), AVI/AVI (insensitive), orPAV/AVI (heterozygotes); subjects with other TAS2R38 haplotypeswere not recruited. Overall, PAV/PAV subjects rated the glucosinolategenerating vegetables as much more bitter than did the AVI/AVIsubjects. Bitterness ratings of non-glucosinolate generating foods, suchas bitter melon, endive, and radicchio, did not differ as a function ofTAS2R38 haplotype with the notable exception of one food.Heterozygous subjects´ vegetable ratings were closer to those ofPAV/PAV than AVI/AVI subjects. These results demonstrate theimportance of individual human taste gene alleles when specific foodpreferences are studied. In this case, a broad family of plants thatproduce compounds containing the N-C=S moiety are perceived asespecially bitter by people who possess even a single `sensitive´ alleleof only one bitter taste receptor gene. This work was supported by agrant from NIH DC02995 and P50 DC0670 to P.A.S.B158 Slide Taste ChemoreceptionINFLUENCE OF RESPONSE VARIABILITY ON THE CODINGPERFORMANCE OF CENTRAL GUSTATORY NEURONSLemon C.H. 1 , Smith D.V. 1 1 Anatomy and Neurobiology, University ofTennessee, Memphis, TNWe explored how variability in responding to taste stimuli couldimpact the ability of central gustatory neurons to signal taste quality.Taste responses to (in M) 0.5 sucrose, 0.1 NaCl, 0.01 HCl and 0.01quinine-HCl were recorded from cells in the nucleus of the solitary tractof anesthetized rats. We attempted to test each neuron 6 times with eachstimulus. On each trial, the instantaneous firing rate (spikes/s) wasrepeatedly sampled during the first 2 s of taste responding to buildhistograms of spike rates for each stimulus. For each neuron, pairs ofhistograms were compared using an analysis based on statisticaldecision theory to estimate the probability (P) that an observer withknowledge of the means of these distributions could discriminatebetween firing rates to different stimuli. This analysis bears on whetherthe mean firing rates to different stimuli are reliably different. Thistechnique was also applied to pairs of distributions between neurons toexplore relative response relationships to tastants. Data from 172 trialsrecorded from 8 neurons of different categories (sucrose-, NaCl- orHCl-oriented) were analyzed. For each cell, a failure to discriminatebetween firing rates to the most effective stimulus and at least one othertastant was found (P < detection threshold). Yet analyses of relativefiring between heterogeneous neurons revealed that different stimuliproduced detectably different response relationships that could be usedto identify stimulus quality. Results suggest that taste quality could besignaled by the relative firing of different kinds of neurons in parallel.Support, NIH DC00353.159 Symposium Trp ChannelsTRP CHANNELS: MEDIATORS OF SENSORY SIGNALINGAND ROLES IN HEALTH AND DISEASEMontell C. 1 1 Biological Chemistry, Johns Hopkins University,Baltimore, MDThe TRP superfamily is distinct from other ion channel families indisplaying an unusually diverse set of activation mechanisms and cationselectivities. However, one unifying theme is that so members of thissuperfamily have critical roles in sensory physiology. The foundingmember of this superfamily, Drosophila TRP, is critical forphototransduction and null mutations in this channel result in lightdependentretinal degeneration. Conversely, constitutive activation ofTRP results in profound cell death. The molecular bases for thedegenerations resulting from either decreased or increased TRP channelactivity will be presented. Influx of Ca 2+ via the TRP channels iscountered by rapid Ca 2+ extrusion and we have found that the primaryextrusion mechanism is via the Na + /Ca 2+ exchanger, CalX. OtherDrosophila members of the TRP family are essential for a variety ofsensory functions and we will describe recent work indicating that theTRPA2 channel functions in the gustatory response. Finally, mutationsin TRP channels underlie a variety of human diseases, such aspolycystic kidney disease and mucolipidosis. We will present our workestablishing Drosophila as an animal model to characterize thesediseases.160 Symposium Trp ChannelsTHERMOTRP CHANNELS AND CHEMESTHESISPatapoutian A. 1 1 Cell Biology, The Scripps Research Institute, La Jolla,CAAbstract: Mechanical forces, chemical stimuli, and temperature areperceived by the sense of touch, but the molecules that mediate thisability have been a long-standing mystery. Temperatures above 43 o Cand capsaicin were shown to activate the ion channel TRPV1 (VR1), amember of Transient Receptor Potential (TRP) family of cationchannels. Taking advantage of the human genome project, we mined foradditional TRP channels. Our work has led to the characterization of awarm-activated TRP channel, TRPV3 (33°C threshold) and two coldactivatedTRP channels, TRPM8 (25°C threshold) and TRPA1 (17°Cthreshold). These ion channels are also the receptors for natural sensorycompounds such as camphor, menthol, allicin, and cinnamaldehyde.We have also shown that the Drosophila sequence orthologue ofTRPA1 is activated by temperature, suggesting an evolutionaryconserved role of TRP channels. We are using a combination of geneticand pharmacological studies to elucidate the role of these ion channelsin vivo.40