Low pH facilitates capsaicin responses in isolated sensory neurons of the rat

Kress, Michaela; Fetzer, S; Reeh, Peter W.; Vyklický, Ladislav

doi:10.1016/0304-3940(96)12691-4

Cited by 47 publications

(35 citation statements)

References 15 publications

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“…Moderate acidification sensitizes its responses to other stimuli such as capsaicin and heat (Petersen and Lamotte, 1993;Martenson et al, 1994;Baumann et al, 1996;Kress et al, 1996;Tominaga et al, 1998). Severe acidification directly activates the channel (Bevan and Yeats, 1991;Tominaga et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Uncoupling Proton Activation of Vanilloid Receptor TRPV1

Ryu¹,

Liu²,

Yao³

et al. 2007

J. Neurosci.

130

147

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Multimodal gating is an essential feature of many TRP ion channels, enabling them to respond to complex cellular environments. TRPV1, a pain receptor involved in nociception at the peripheral nerve terminals, can be activated by a range of physical and chemical stimuli (e.g., capsaicin, proton, and heat) and further sensitized by proinflammatory substances. How a single receptor achieves this multiplicity of functionality is poorly understood at the molecular level. Here, we investigated the structural basis of proton activation of TRPV1. Chimeric channels between rTRPV1 and the low pH-insensitive homolog TRPV2 were constructed by systematically exchanging the extracellular domains and were characterized using whole-cell recording in transiently transfected HEK293 cells. Two discrete domains, one involving the pore helix and the other the S3-S4 linker, were found crucial for direct activation of the channel by low pH. Single residue mutations in either domain (T633A/V538L) abrogated the proton-evoked current while preserving the capsaicin and heat responses and their potentiation by mildly acidic pH. Both residues exert a gating effect through hydrophobic interactions. Our results unravel novel information on the structural basis of channel function, and support the existence of discrete domains for multimodal gating of the channel. In view of the resemblance of the pore of TRPV1 to KcsA, our findings also provide evidence on the pore helix as an active component in channel gating in addition to its role in ion permeation.

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Section: Introductionmentioning

confidence: 99%

Uncoupling Proton Activation of Vanilloid Receptor TRPV1

Ryu¹,

Liu²,

Yao³

et al. 2007

J. Neurosci.

130

147

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“…Changes in the pH in the (patho)physiological range can modulate the ability of capsaicin to activate TRPV1 (Kress et al, 1996;Tominaga et al, 1998;McLatchie and Bevan, 2001). Acidification to pH Ͻ6.5 can also activate TRPV1 at room temperature by lowering the thermal threshold for activation (Tominaga et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

TRPM8 Activation by Menthol, Icilin, and Cold Is Differentially Modulated by Intracellular pH

Andersson

Chase²,

Bevan

2004

Journal of Neuroscience

181

139

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TRPM8 is a nonselective cation channel activated by cold and the cooling compounds menthol and icilin (Peier et al., 2002] from pH 7.3 to approximately pH 6 abolished responses to icilin and cold stimulation but did not affect responses to menthol. Icilin concentrationresponse curves were significantly shifted to the right when pH was lowered from 7.3 to 6.9, whereas those with menthol were unaltered in solutions of pH 6.1. When cells were exposed to solutions in the range of pH 8.1-6.5, the temperature threshold for activation was elevated at higher pH and depressed at lower pH. Superfusing cells with a low subactivating concentration of icilin or menthol elevated the threshold for cold activation at pH 7.4, but cooling failed to evoke [Ca 2ϩ ] i responses at pH 6 in the presence of either agonist. In voltage-clamp experiments in which the intracellular pH was buffered to different levels, acidification reduced the current amplitude of icilin responses and shifted the threshold for cold activation to lower values with half-maximal inhibition at pH 7.2 and pH 7.6.The results demonstrate that the activation of TRPM8 by icilin and cold, but not menthol, is modulated by intracellular pH in the physiological range. Furthermore, our data suggest that activation by icilin and cold involve a different mechanism to activation by menthol.

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“…Previously, acidification was noted to sensitize nociceptive neurons toward vanilloids (40,41) and eicosanoids including, but probably not confined to, PGE 2 and prostacyclin (18,20,21,42,43). In addition to acid-sensitive sodium ion channels (44 -46), recent point mutation studies implicate H ϩ as a direct regulator of VR1.…”

Section: Vanilloid Receptor 1 Activation By H ϩ and Eicosanoidsmentioning

confidence: 99%

Anandamide Activates Vanilloid Receptor 1 (VR1) at Acidic pH in Dorsal Root Ganglia Neurons and Cells Ectopically Expressing VR1

Oláh

Karai

Iadarola

2001

Journal of Biological Chemistry

123

110

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The vanilloid receptor type 1 (VR1) is a heat-activated ionophore preferentially expressed in nociceptive neurons of trigeminal and dorsal root ganglia (DRG). VR1, which binds and is activated by capsaicin and other vanilloid compounds, was noted to interact with the endocannabinoid anandamide (ANA) and certain inflammatory metabolites of arachidonic acid in a pH-dependent manner. At pH < 6.5 ANA induced

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Low pH facilitates capsaicin responses in isolated sensory neurons of the rat

Cited by 47 publications

References 15 publications

Uncoupling Proton Activation of Vanilloid Receptor TRPV1

Uncoupling Proton Activation of Vanilloid Receptor TRPV1

TRPM8 Activation by Menthol, Icilin, and Cold Is Differentially Modulated by Intracellular pH

Anandamide Activates Vanilloid Receptor 1 (VR1) at Acidic pH in Dorsal Root Ganglia Neurons and Cells Ectopically Expressing VR1

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