Activation of TRPA1 by membrane permeable local anesthetics.

ABSTRACT:

Background

Low concentrations of local anesthetics (LAs) suppress cellular excitability by inhibiting voltage-gated Na⁺ channels. In contrast, LAs at high concentrations can be excitatory and neurotoxic. We recently demonstrated that LA-evoked activation of sensory neurons is mediated by the capsaicin receptor TRPV1, and, to a lesser extent by the irritant receptor TRPA1. LA-induced activation and sensitization of TRPV1 involves a domain that is similar, but not identical to the vanilloid-binding domain. Additionally, activation of TRPV1 by LAs involves PLC and PI(4,5)P₂-signalling. In the present study we aimed to characterize essential structural determinants for LA-evoked activation of TRPA1.

Results

Recombinant rodent and human TRPA1 were expressed in HEK293t cells and i

SUBMITTER: Leffler A 

PROVIDER: S-EPMC3179737 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature