Abstract
Acid-sensing ion channels (ASICs) are neuronal H+-gated cation channels, and the transient receptor potential vanilloid 1 channel (TRPV1) is a multimodal cation channel activated by low pH, noxious heat, capsaicin, and voltage. ASICs and TRPV1 are present in sensory neurons. It has been shown that raising the temperature increases TRPV1 and decreases ASIC H+-gated current amplitudes. To understand the underlying mechanisms, we have analyzed ASIC and TRPV1 function in a recombinant expression system and in dorsal root ganglion (DRG) neurons at room and physiological temperature. We show that temperature in the range studied does not affect the pH dependence of ASIC and TRPV1 activation. A temperature increase induces, however, a small alkaline shift of the pH dependence of steady-state inactivation of ASIC1a, ASIC1b, and ASIC2a. The decrease in ASIC peak current amplitudes at higher temperatures is likely in part due to the observed accelerated open channel inactivation kinetics and for some ASIC types to the changed pH dependence of steady-state inactivation. The increase in H+-activated TRPV1 current at the higher temperature is at least in part due to a hyperpolarizing shift in its voltage dependence. The contribution of TRPV1 relative to ASICs to H+-gated currents in DRG neurons increases with higher temperature and acidity. Still, ASICs remain the principal pH sensors of DRG neurons at 35°C in the pH range ≥6.
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Abbreviations
- AP:
-
Action potential
- ASIC:
-
Acid-sensing ion channel
- BCTC:
-
4-(3-Chloro-2-pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide
- CHO:
-
Chinese hamster ovary
- DRG:
-
Dorsal root ganglia
- ENaC:
-
Epithelial sodium channel
- HEK:
-
Human embryonic kidney
- nH :
-
Hill number
- pH0.5 :
-
pH of half-maximal activation
- pHIn0.5 :
-
pH of half-maximal inactivation
- SSIN:
-
Steady-state inactivation
- τ I :
-
Time constant of open channel inactivation
- τ R :
-
Time constant of recovery from inactivation
- TRPV1:
-
Transient receptor potential vanilloid 1
- V 0.5 :
-
Voltage of half-maximal conductance
- V m :
-
Membrane potential
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Acknowledgments
We thank Laurent Schild, Aurélien Boillat, Benoîte Bargeton, Cedric Laedermann, Olivier Poirot, and Miguel van Bemmelen for their comments on a previous version of the manuscript and for many discussions. This research was supported by grant 31003A0-117717 of the Swiss National Science Foundation to S.K.
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The authors declare that they have no conflict of interest.
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Blanchard, M.G., Kellenberger, S. Effect of a temperature increase in the non-noxious range on proton-evoked ASIC and TRPV1 activity. Pflugers Arch - Eur J Physiol 461, 123–139 (2011). https://doi.org/10.1007/s00424-010-0884-3
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DOI: https://doi.org/10.1007/s00424-010-0884-3