G proteins activate ATP-sensitive K+ channels by antagonizing ATP-dependent gating.
To determine whether G proteins activate cardiac ATP-sensitive K+ (KATP) channels by regulating intracellular ATP (ATPi)-dependent gating, currents were measured in inside-out patches. When ATPi closed KATP channels, activators of endogenous G proteins, GTP (plus adenosine or acetylcholine), GTP gamma S, or AlF-4 stimulated channels, an effect prevented by GDP beta S. In the absence of ATPi, G protein activators were ineffective. Intracellular nucleoside diphosphates restored KATP channel openings after the "rundown" of spontaneous activity. Only when ATPi suppressed nucleoside diphosphate-induced openings, GTP gamma S or AlF-4 enhanced KATP channel activity. Active forms of exogenous G protein subunits (G alpha i-1, G alpha i-2, or G alpha o) activated only KATP channels closed by ATPi. G proteins stimulate cardiac KATP channels apparently by antagonizing ATPi-dependent inhibitory gating. Regulation of ligand-dependent gating represents a distinct type of G protein modulation of ion channels.
Terzic
A
A
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.
Tung
R T
RT
Inanobe
A
A
Katada
T
T
Kurachi
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D007290:Inosine Diphosphate / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D014530:Uridine Diphosphate / Q000494:pharmacology
D017607:Aluminum Compounds; D015221:Potassium Channels; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014530:Uridine Diphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); D006160:Guanosine Triphosphate; D007290:Inosine Diphosphate; D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins; D000241:Adenosine; D000109:Acetylcholine; D005459:Fluorides; C032311:aluminum fluoride