Camphor modulates TRPV3 cation channels activity by interacting with critical pore-region cysteine residues.

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Sherkheli MA, Vogt-Eisele AK, Weber K, Hatt H

Camphor modulates TRPV3 cation channels activity by interacting with critical pore-region cysteine residues.

Pak J Pharm Sci. 2013 May;26(3):431-8.

PubMed ID

23625413 [ View in PubMed

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Abstract

TRPV3 ion channels mediate thermo-transduction, nociception, inflammation and dermatitis in mammals. TRPV1-4 proteins have been shown to have conserved cysteine-residues in the pore-forming regions. These residues participate in channel activation via S-nitrosylation of channel proteins. Camphor is a commonly used ligand for TRPV3 channels. Thus the knowledge about the potential binding/interacting site(s) for camphor will help to design effective and potent analgesic compounds. In an overlap-extension PCR method, following primer-pairs were used to mutate conserved cysteine-residues in the pore-region of TRPV3 channels; GATTGAGAATcCTCCAAGGACAAAAAGGAC, TRPV3-C612S-Fw and GTCCTTGGAGgACTTCTCAATCAGTCAGTGAGG, TRPV3-C612S-Rv primers pair. And for TRPV3-C619S: GGACTCcAGTTCCTATGGCCAGC, TRPV3-C619S-Fw and GCTGGCCATAgGAACTGGAGTCC, TRPV3-C619S-Rv respectively. All cDNA constructs were confirmed by DNA-sequencing and used to make cRNAs. Oocytes expressing mTRPV3-C619S and mTRPV3-C612S mutant channels were challenged with 2-APB (1 mM), camphor (10 mM) and dihydrocarveol (10 mM) either at -40 mV or +40 mV holding potentials in voltage-clamp experiments. Responses of both mutants to 2-APB were similar to wild-type mTRPV3. Interestingly, responses to camphor were totally lost in mTRPV3-C619S mutant, while responses to dihydrocarveol remained intact. In contrast mTRPV3-C612S displayed slightly altered (16+/-2 % reduction) phenotype with respect to camphor sensitivity. It is concluded that pore-region cysteines play critical role in camphor sensitivity of TRPV3 ion channels.

DrugBank Data that Cites this Article

Drugs

(S)-camphor

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
(S)-camphor	Transient receptor potential cation channel subfamily V member 3	Protein	Humans	Yes	Agonist Activator	Details
Camphor	Transient receptor potential cation channel subfamily V member 3	Protein	Humans	Yes	Agonist Activator	Details