Painless Without ATP

Abstract

The capsaicin receptor (CAP) is a cation channel involved in pain perception. Kwak et al. observed that when inside-out patches are prepared from dorsal root ganglia neurons for electrophysiological recording, the CAP activity is reduced, indicating that an intracellular regulator may be lost in the inside-out preparation. Adenosine trisphosphate (ATP) was found to enhance ICAP in response to application of capsaicin by a mechanism that did not require ATP hydrolysis and was not inhibited by treatments to block a variety of protein kinases. CAP has two putative nucleotide-binding domains and mutations in either of these domains eliminates the ability of ATP to enhance channel activity in response to capsaicin. The data suggest that ATP is an endogenous regulator of CAP. The KD for ATP to influence ICAP is within the range that would allow the ATP sites to be continuously occupied in vivo under normal conditions, but may be a mechanism for modulating pain perception during periods of cellular stress, such as ischemia.Kwak, J., Wang, M.H., Hwang, S.W., Kim, T.-Y., Lee, S.-Y., and Oh, U. (2000) Intracellular ATP increases capsaicin-activated channel activity by interacting with nucleotide binding domains. J. Neurosci. 20: 8298-8304. [Abstract] [Full Text]