title: Functional interaction between K(ATP) channels and the Na(+)-K(+) pump in metabolically inhibited heart cells of the guinea-pig.
abstract: 1. Transmembrane current through ATP-regulated K(+) channels (IK(ATP)) was measured in ventricular heart cells of the guinea-pig in the whole-cell and cell-attached patch configurations under conditions of metabolic poisoning with the mitochondrial uncoupler 2,4-dinitrophenol (DNP). 2. Maintained exposure of the cells to DNP resulted in a transient appearance of whole-cell IK(ATP) When IK(ATP) had reached several nanoamps, blocking the forward-running Na(+)-K(+) pump with 0.5 mM strophanthidin decreased IK(ATP) after a delay. The time course of this decrease could be described by a single exponential function, which yielded a time constant(T)of 4.51+/- 1.89 s (n=8). 3. Hyperpolarization from 0 mV to -100 or -150 mV for 2 s caused IK(ATP) (measured at 0 mV) to decrease by 34.2 +/- 14.1 % (n = 8) and 37.6 +/- 9.4% (n = 8), respectively. After the hyperpolarizing pulse, IK(ATP) returned to its higher initial level within a couple of seconds. 4. Driving the pump backwards by removing the extracellular K(+) ions caused the permanent disappearance of DNP-induced IK(ATP). 5. Application of 0.5 mM strophanthidin in the absence of external K(+) ions induced a transient increase in IK(ATP), as did washing out the glycoside (n = 5). 6. When pump action was inhibited by using Na(+), K(+)-free Tyrode solution (see Methods) in the bath, strophanthidin did not have a comparable direct effect on IK(ATP). 7. In cell-attached patches, strophanthidin applied via the bath caused a reduction in IK(ATP) with a similar time course to that in whole-cell experiments. This suggests that the interaction between the pump molecules and the K(ATP) channels is not restricted to closely neighbouring molecules. 8. The data support the hypothesis that [ATP] at the cytosolic face of the membrane may drop to practically zero, thereby passing an 'ATP window' in which the channels first open and then close, and that the submembrane [ATP] is readily controlled by the cytosolic [ATP].
authors.affiliation: Zentrum für Physiologie, Universität zu Köln, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Priebe
authors.forename: M
authors.initials: M
authors.lastname: Friedrich
authors.forename: K
authors.initials: K
authors.lastname: Benndorf
mesh_terms: D019297:2,4-Dinitrophenol / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D013327:Strophanthidin / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology*
chemical_list: D015221:Potassium Channels; D014475:Uncoupling Agents; D013327:Strophanthidin; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D019297:2,4-Dinitrophenol; D011188:Potassium