Intracellular ADP-ribose inhibits ATP-sensitive K+ channels in rat ventricular myocytes.
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.
Kwak
Y G
YG
Department of Pharmacology, Chonbuk National University Medical School, Chonju, South Korea.
Park
S K
SK
Kim
U H
UH
Han
M K
MK
Eun
J S
JS
Cho
K P
KP
Chae
S W
SW
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D036563:Cyclic ADP-Ribose; D006352:Heart Ventricles; D007425:Intracellular Membranes / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D000255:Adenosine Triphosphate