PT  - JOURNAL ARTICLE
AU  - Jiyeon Kwak
AU  - Myeong Hyeon Wang
AU  - Sun Wook Hwang
AU  - Tae-Yoon Kim
AU  - Soon-Youl Lee
AU  - Uhtaek Oh
TI  - Intracellular ATP Increases Capsaicin-Activated Channel Activity by Interacting with Nucleotide-Binding Domains
AID  - 10.1523/JNEUROSCI.20-22-08298.2000
DP  - 2000 Nov 15
TA  - The Journal of Neuroscience
PG  - 8298--8304
VI  - 20
IP  - 22
4099  - http://www.jneurosci.org/content/20/22/8298.short
4100  - http://www.jneurosci.org/content/20/22/8298.full
SO  - J. Neurosci.2000 Nov 15; 20
AB  - Capsaicin (CAP)-activated ion channel plays a key role in generating nociceptive neural signals in sensory neurons. Here we present evidence that intracellular ATP upregulates the activity of capsaicin receptor channel. In inside-out membrane patches isolated from sensory neurons, application of CAP activated a nonselective cation channel (icap). Further addition of ATP to the bath caused a significant increase inicap , with aK1/2 of 3.3 mm. Nonhydrolyzable analogs of ATP, adenylimidodiphosphate and adenosine 5′-O-(3-thio)-triphosphate, also increasedicap . Neither Mg2+-free medium nor inhibitors of various kinases blocked the increase in icap induced by ATP. The enhancing effect of ATP was also observed in inside-out patches of oocytes expressing vanilloid receptor 1, a cloned capsaicin receptor. Single point mutations (D178N, K735R) within the putative Walker type nucleotide-binding domains abolished the effect of ATP. These results show that ATP increasesicap in sensory neurons by direct interaction with the CAP channel without involvement of phosphorylation.