Role of the inward rectifier IK1 in the myocardial response to hypoxia.

Study Objective: The aim was to assess the contribution of the inward rectifier IK1 to the electrical responses of the myocardium to hypoxia: action potential shortening, maintenance of resting potential, and myocardial K loss.

Design: Hypoxia induced changes of gK1 were inferred from the effects of 40 microns Ba2+ on action potential duration, resting potential, and cellular K content of normoxic and hypoxic rabbit hearts paced at 2.5 Hz and perfused at 33 degrees C and constant coronary flow of 20 ml.min-1. The components (diffusion generated and Na pump related) of the resting potential (Vr) were separated by exposure to 10(-4) M ouabain. The effects of varying the extracellular K concentration (Ko) were also examined.

Experimental Material: New Zealand rabbits were heparinised and anaesthetised and the hearts rapidly excised and perfused in the Langendorff manner.

Measurements And Main Results: The membrane potential was measured with standard glass microelectrodes and the cellular content of K and Na estimated from determinations of total electrolyte and water content and volume of the inulin space of the tissue. In normoxia, Ba2+ caused a slight depolarisation at Ko below 10 mM and lengthened the action potential duration at 95% repolarisation (APD95) without altering the plateau duration. In hypoxia, Ba2+ caused further depolarisation and markedly reduced the APD95 shortening at normal Ko. The Vr v Ko relationship was considerably flattened and the diffusion component of Vr became insensitive to changes in Ko between 1.5 and 10 mM. Concomitantly, the Na pump related fraction of Vr increased under Ba2+. Barium also attenuated myocardial K loss induced by hypoxia.

Conclusion: Our data suggest that an increase in the IK1 current underlies the maintenance of Vr in hypoxia despite the decrease in the transmembrane K gradient and contributes to the action potential shortening, speeding up the late repolarisation. The inwardly rectifying K channels would also be involved in the increased efflux of K+. In contrast, the decrease in plateau duration is probably caused by another K current system, less sensitive to Ba2+. Finally, the contribution of electrogenic Na pumping to Vr becomes critical for the maintenance of the resting potential under conditions of decreased resting permeability.