Anoxia decreases the transient K+ outward current in isolated ventricular heart cells of the mouse.
Transient K+ outward currents (Ito) were measured in enzymatically isolated ventricular mouse heart cells with a patch clamp technique in the whole cell configuration. Exposure of the cells to substrate-free anoxia gradually decreased both the peak and the late Ito. The inactivation time course of Ito was fitted with two exponentials. After 4-10 min of anoxia, the contribution of the fast and slow exponential decreased to 60 +/- 7% and 62 +/- 4% of the control value and recovered after reoxygenation within 1-3 min to 84 +/- 5% and 75 +/- 6% (n = 10; all mean +/- SEM), respectively. The time constants of the exponentials were invariant to anoxia. Voltage dependence of activation and inactivation of Ito were not influenced by anoxia. Application of stimulators of protein kinase A and C, cGMP- dependent protein kinase, or of the oxidant diamide during anoxia did not recover Ito. It is concluded that under conditions of metabolic stress, Ito is reversibly down-regulated leaving inactivation kinetics unchanged. The underlying mechanism is as yet unknown but does neither involve a decreased activity of protein kinase A, protein kinase C, nor c-GMP dependent protein kinase.
Institut für Vegetative Physiologie, Universität zu Köln, Germany.
S
S
Thierfelder
H
H
Hirche
K
K
Benndorf
D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D004594:Electrophysiology; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D015221:Potassium Channels