1. Mouse ventricular myocytes develop a large transient K+ outward current (ITO) which accelerates repolarization and is a crucial determinant for the regulation of the action potential duration at various heart rates. The effect of 3-hydroxybutyrate on ITO was investigated under voltage-and current-clamp conditions. 2. The drug blocked ITO in a stereoselective manner with the L-enantiomer being the effective and the D-enantiomer, the ineffective form. The blocking action of the L-enantiomer was established immediately and it could be completely washed out within several tens of seconds.3. The dose-response characteristic for the peak ITO showed a strict 1: 1 binding of the drug to the receptor with a concentration of half-maximum effect of 2 1 mmol F'.4. The action of L-hydroxybutyrate was voltage independent, did not need channel opening and preferentially affected the slow component of both inactivation and recovery from inactivation. 5. At the high concentration of 20 mmol F1 the optically inactive form, the racemate, did not affect ITO, indicating that the ineffective D-enantiomer interacts with the channels at much lower concentrations.6. At a concentration of 10 mmol F', L-hydroxybutyrate prolonged the action potential by 218 + 26 and 127 + 10% (means + S.E.M.) at 50 and 90% repolarization, respectively. 7. It is concluded that the non-physiological L-hydroxybutyrate is a novel type of blocker of ITO It interacts either with the channel itself, or with a receptor protein closely related to the channel and preferentially affects slow inactivation.

In ventricular myocardial cells of the guinea pig and the mouse, anoxia caused after a mean latency of 439 _+ 141 s and 129 _+ 23 s (mean _ S.E.M.), respectively, a large current through KgTp-channels. This current disappeared within several seconds when reoxygenating the cells but decayed also completely at maintained anoxia. The kinetics of the latter process, however, were much slower and obeyed an approximately monoexponential time course with time constants in the range of 30 s. The results suggest that in the ischaemic myocardium KATp-channels contribute only to the initial phase of extracellular K + accumulation.

No abstract

The activity of K(ATP) channels in cardiomyocytes of mice is controlled by a cytosolic [ATP] pool for which oxidative phosphorylation is the predominant ATP source.

In isolated heart cells, maintained anoxia causes a transient opening of KATP channels. In the ischemic myocardium, this extra K+ conductance results in a decreased contractility and may be arrhythmogenic. Recent studies provide further evidence that the transient activity of KATP channels during anoxia is correlated with the time course of extracellular K+ accumulation during ischemia.