TY - JOUR
T1 - Intracellular ATP increases capsaicin-activated channel activity by interacting with nucleotide-binding domains
AU - Kwak, J.
AU - Myeong Hyeon Wang, Hyeon Wang
AU - Sun Wook Hwang, Wook Hwang
AU - Kim, T. Y.
AU - Lee, S. Y.
AU - Oh, U.
PY - 2000/11/15
Y1 - 2000/11/15
N2 - 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 (i(cap)). Further addition of ATP to the bath caused a significant increase in i(cap), with a K(1/2) of 3.3 mM. Nonhydrolyzable analogs of ATP, adenylimidodiphosphate and adenosine 5'-O-(3-thio)-triphosphate, also increased i(cap). Neither Mg2+-free medium nor inhibitors of various kinases blocked the increase in i(cap) 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 increases i(cap) in sensory neurons by direct interaction with the CAP channel without involvement of phosphorylation.
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 (i(cap)). Further addition of ATP to the bath caused a significant increase in i(cap), with a K(1/2) of 3.3 mM. Nonhydrolyzable analogs of ATP, adenylimidodiphosphate and adenosine 5'-O-(3-thio)-triphosphate, also increased i(cap). Neither Mg2+-free medium nor inhibitors of various kinases blocked the increase in i(cap) 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 increases i(cap) in sensory neurons by direct interaction with the CAP channel without involvement of phosphorylation.
KW - ATP
KW - Allosteric regulation
KW - Capsaicin receptor
KW - Nucleotide-binding motif
KW - Pain
KW - VR1
UR - http://www.scopus.com/inward/record.url?scp=0034668893&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.20-22-08298.2000
DO - 10.1523/jneurosci.20-22-08298.2000
M3 - Article
C2 - 11069936
AN - SCOPUS:0034668893
VL - 20
SP - 8298
EP - 8304
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 22
ER -