K+ channels and metabolic inhibition in cardiac cells.
Metabolic inhibition, whether it is caused by ischemia or hypoxia, is characterized by an important net K+ outward movement. The nature of the currents involved remains a subject of discussion. Good candidates among the many representatives of the large K+ channel family are the ATP-dependent and the Nai-activated K+ channels. Arguments in favour of the ATP-dependent K+ channel will be presented and are based on: 1) the effect of oral antidiabetics on action potential duration during hypoxia; 2) an estimation of the proportion of channels that need to be activated; the channel itself can be activated at relatively high ATP concentrations, and 3) the rectifying properties of the activated current at the whole cell and single channel level. A Nai(+)-activated K+ current can be induced by intracellular dialysis with a solution containing a high Nai+ concentration. Induction is facilitated by simultaneous blockade of the Na+, K+ pump with ouabain or Ke(+)-free solution superfusion. The current shows marked outward rectifying properties. At the single channel level, the open probability was dependent on Nai+ and Na+, K+ pump activity. The channel showed inward rectification when Ki+ less than Ke+, but outward rectification when Ki+ greater than Ke+. The channel and the whole cell current showed similar blocking phenomena. The Nai(+)-activated K+ current may play an important role in action potential shortening during pump blockade and be responsible for a marked K+ loss in advanced ischemia.
Carmeliet
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E
Laboratory of Physiology, University Leuven, Belgium.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005905:Glyburide / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D012964:Sodium; D005905:Glyburide