The biophysical and molecular basis of TRPV1 proton gating
| Autor: | Stephen C. Phillips, Lishuang Cao, Marianthi Papakosta, Eduardo Aneiros, Edward B. Stevens, Christian Grimm |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Membrane potential
General Immunology and Microbiology Proton musculoskeletal neural and ocular physiology General Neuroscience TRPV1 Long-term potentiation Gating Biology General Biochemistry Genetics and Molecular Biology Transient receptor potential channel chemistry.chemical_compound nervous system Biochemistry chemistry Capsaicin Biophysics lipids (amino acids peptides and proteins) Patch clamp Molecular Biology |
| Zdroj: | The EMBO Journal. 30:994-1002 |
| ISSN: | 0261-4189 |
| DOI: | 10.1038/emboj.2011.19 |
| Popis: | The capsaicin receptor TRPV1, a member of the transient receptor potential family of non-selective cation channels is a polymodal nociceptor. Noxious thermal stimuli, protons, and the alkaloid irritant capsaicin open the channel. The mechanisms of heat and capsaicin activation have been linked to voltage-dependent gating in TRPV1. However, until now it was unclear whether proton activation or potentiation or both are linked to a similar voltage-dependent mechanism and which molecular determinants underlie the proton gating. Using the whole-cell patch-clamp technique, we show that protons activate and potentiate TRPV1 by shifting the voltage dependence of the activation curves towards more physiological membrane potentials. We further identified a key residue within the pore region of TRPV1, F660, to be critical for voltage-dependent proton activation and potentiation. We conclude that proton activation and potentiation of TRPV1 are both voltage dependent and that amino acid 660 is essential for proton-mediated gating of TRPV1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text