AJP - Cell Physiology, Vol 271, Issue 2 C464-C468, Copyright © 1996 by American Physiological Society
Intracellular ADP-ribose inhibits ATP-sensitive K+ channels in rat ventricular myocytes
Y. G. Kwak, S. K. Park, U. H. Kim, M. K. Han, J. S. Eun, K. P. Cho and S. W. Chae
Department of Pharmacology, Chonbuk National University Medical School, Chonju, South Korea.
Cyclic ADP-ribose (cADPR), an NAD metabolite, has been shown to be a
messenger for Ca2+ mobilization from intracellular Ca2+ stores. However,
the physiological role of ADP-ribose (ADPR), another metabolite of NAD, is
not known. We examined the effects of cADPR and ADPR on the ATP-sensitive
K+ channel (KATP) activity in rat ventricular myocytes by use of the
inside-out patch-clamp configuration. ADPR, but not cADPR, inhibited the
channel activity at micromolar range with an inhibitor constant (Ki) of
38.4 microM. The Hill coefficient was 0.9. ATP inhibited the K+ channel
with a Ki of 77.8 microM, and the Hill coefficient was 1.8. Single-channel
conductance was not affected by ADPR. These findings strongly suggest that
ADPR may act as a regulator of KATP channel activity.
