Identification of a putative binding site critical for general anesthetic activation of TRPA1.

ABSTRACT: General anesthetics suppress CNS activity by modulating the function of membrane ion channels, in particular, by enhancing activity of GABA_A receptors. In contrast, several volatile (isoflurane, desflurane) and i.v. (propofol) general anesthetics excite peripheral sensory nerves to cause pain and irritation upon administration. These noxious anesthetics activate transient receptor potential ankyrin repeat 1 (TRPA1), a major nociceptive ion channel, but the underlying mechanisms and site of action are unknown. Here we exploit the observation that pungent anesthetics activate mammalian but not Drosophila TRPA1. Analysis of chimeric Drosophila and mouse TRPA1 channels reveal a critical role for the fifth transmembrane domain (S5) in sensing anesthetics. Interestingly,

SUBMITTER: Ton HT 

PROVIDER: S-EPMC5389314 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature