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Review
. 2015 Feb 11;2(2):214-26.
doi: 10.1080/23328940.2014.1000702. eCollection 2015 Apr-Jun.

Species-specific temperature sensitivity of TRPA1

Willem J Laursen  1 , Evan O Anderson  2 , Lydia J Hoffstaetter  1 , Sviatoslav N Bagriantsev  2 , Elena O Gracheva  1
Affiliations
Review

Species-specific temperature sensitivity of TRPA1

Willem J Laursen et al. Temperature (Austin). .

Abstract

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal ion channel sensitive to temperature and chemical stimuli. The importance of temperature and aversive chemical detection for survival has driven the evolutionary diversity of TRPA1 sensitivity. This diversity can be observed in the various roles of TRPA1 in different species, where it is proposed to act as a temperature-insensitive chemosensor, a heat transducer, a noxious cold transducer, or a detector of low-intensity heat for prey localization. Exploring the variation of TRPA1 functions among species provides evolutionary insight into molecular mechanisms that fine-tune thermal and chemical sensitivity, and offers an opportunity to address basic principles of temperature gating in ion channels. A decade of research has yielded a number of hypotheses describing physiological roles of TRPA1, modulators of its activity, and biophysical principles of gating. This review surveys the diversity of TRPA1 adaptations across evolutionary taxa and explores possible mechanisms of TRPA1 activation.

Keywords: AITC- allyl isothiocyanate; ANKTM1; ANKTM1- ankyrin-like with transmembrane domains protein 1; AR- ankyrin repeat; EC50- half maximal effective concentration; Ion channels; Keq- equillibrium constant; PH- pore helix; PI- phosphatidylinositol; Q10- temperature activation coefficient; S1-S6- transmembrane helices 1–6; TRP- Transient Receptor Potential; TRPA1; TRPA1- transient receptor potential ankyrin 1; TRPM8- transient receptor potential melastatin 8; TRPV1- transient receptor potential vanilloid 1; ThermoTRP; Thermosensation; ceTRPA1- Caenorhabditis elegans TRPA1; dTRPA1- Drosophila melanogaster TRPA1; hsTRPA1- hymenoptera-specific TRPA1; ΔCp -change in heat capacity.

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Figures

Figure 1.
Figure 1.
Activators of TRPA1 channel. TRPA1 depicted along with several activators of the channel. TRPA1 is sensitive to temperature and, depending on the ortholog, activates in response to either cold or heat. TRPA1 also responds to pungent plant compounds such as thiosulfinates (onion), Δ9-tetrahydrocannabinol (cannabis, marijuana), allyl isothiocyanate (AITC; wasabi, mustard), cinnamaldehyde (cinnamon), gingerol (ginger), allicin and diallyl disulfide (garlic), and oleocanthal (olive oil). Additionally, the channel can be activated by electrophiles in the environment, including tear gas, toluene, α, β-aldehydes such as acrolein and crotonaldehyde (smoke), and endogenous molecules like 4-hydroxynonenal (4-HNE), hydrogen peroxide (H2O2), and 15-deoxy-δ(12,14)-prostaglandin J2 (15-deoxyΔ PGJ2).
Figure 2.
Figure 2.
Topology diagram of functional domains of TRPA1. Topology diagram of TRPA1, highlighting domains implicated in thermosensation and electrophile-reactive cysteines (yellow circles). (A) Pre-AR N-terminal domain (blue) is suspected to suppress heat activation of dTRPA(A). (B) AR 3-8 (pink) contribute to heat activation of rattlesnake TRPA1; AR 6 is specifically important for heat sensitivity in mouse and fly TRPA1. (C) AR 10-15 (dark red) from both rattlesnake and fly TRPA1 is a portable heat sensitive module. (D) Only fly TRPA1 isoforms with TRP ankyrin cap (red) are activated in response to heat. (E) G878 in S5 (light orange) is necessary for cold activation of rat TRPA1. (F) Point mutation of R1073 or N1066 and I1067 in PH (orange) eliminate heat activation of fly TRPA1. (G) Point mutation of L1105 and I1106 in S6 (orange red) abolish heat sensitivity of fly TRPA1.
Figure 3.
Figure 3.
Interspecies differences in temperature sensitivities of TRPA1 orthologues. Temperature that evokes detectable channel activation (Tact) is listed. Common name refers to TRPA1 orthologues cloned from the following species: Clawed frog-Xenopus tropicalis; Chicken-Gallus gallus domesticus; Ratsnake-Elaphe obsoleta lindheimeri; Anole-Anolis carolinensis; Python-Python regius; Boa-Corallus hortulanus; Rattlesnake-Crotalus atrox; Fruitfly-Drosophila melanogaster; Mosquito-Anopheles gambiae; Nematode-Caenorhabditis elegans; Mouse-Mus musculus; Human-Homo sapiens. Images of ratsnake, rattlesnake, boa, mosquito and human were adapted from Wikimedia Commons (boa image by Geoff Gallice).
Figure 4.
Figure 4.
Electrophysiological analyses of TRPA1 function. (A) Exemplar 2-electrode voltage clamp recordings from Xenopus oocytes expressing human (h), Drosophila (d), or rattlesnake (sn) TRPA1. Currents were elicited by a 2s voltage ramp from −150 to +90 mV from a holding potential of −80 mV, in standard ND96 solution (final concentration, mM: 2 KCl, 96 NaCl, 20 MgCl2, 1.8 CaCl2, 5 HEPES pH 7.4) at 36°C (red), 4°C (blue), and/or in the presence of 1 mM AITC (green). (B) Exemplar temperature responses of human (h, green), Drosophila (d, red), and rattlesnake (sn, blue) TRPA1 orthologues recorded at different temperatures and measured at +80 mV as described in (A). (C) Exemplar responses of human TRPA1 (black) and uninjected oocytes (red) to cooling, heating and AITC (1mM) measured at +80mV.
Figure 5.
Figure 5.
Two models predict ion channel activation by heat and cold. Equilibrium constant is nonmonotonic with temperature given positive ΔCp (here, 2kcal/mol-K) under the thermodynamics relationship: ln(Keq(T))=ΔS0°−ΔCp[1−T0T+ln(T0T)]R. Given ΔS° at temperature of minimal Keq of −9 cal/mol*K, setting minimal temperature of channel opening (T0) at 32°C results in a cold-activated channel under physiological conditions while setting T0 (blue) at 15°C results in a heat-activated channel under physiological conditions (red). A shift in T0 could account for interspecies temperature sensitivity differences of TRPA1. Allosteric gating of heat sensitive modules to the channel gate, as proposed by Jara-Oseguera and Islas, yields a similar nonmonotonicity without a requirement for large change in channel heat capacity.
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