Role of Na-activated K channel, Na-K-Cl cotransport, and Na-K pump in [K]e changes during ischemia in rat heart.
The contribution of Na-activated K channel, the furosemide-sensitive (Na-K-Cl) cotransport, and Na-K pump to extracellular potassium accumulation during global ischemia was investigated using pharmacological blockade of these pathways. R 56865 (a blocker of the Na-activated K channel), furosemide, or ouabain was included in the perfusate before ischemia in the isolated rat heart preparation, and the extracellular K concentration ([K]e) was monitored during 30 min of global ischemia. In control hearts, [K]e showed an early rise (up to 9.0 +/- 0.2 mM from the baseline of 5.9 mM), a fall (to a minimum of 6.7 +/- 0.2 mM), and a late rise (to 14.1 +/- 0.4 mM by the end of ischemia). R 56865 (0.1 and 1 microM) suppressed the early [K]e rise to 50% of the control level. The late rise in [K]e was also significantly suppressed by the higher dose of R 56865. Furosemide (0.1 and 1 mM) reduced the early K accumulation by 35% but did not affect the rise of [K]e during the late ischemic phase. Blockade of Na-K pump by 10 microM ouabain did not increase [K]e during any phase of ischemia and, in fact, 100 microM ouabain profoundly suppressed the early rise in [K]e. We therefore suggest that the Na-activated K channel, the furosemide-sensitive cotransport, and changes in the activity of the Na-K pump may all contribute to extracellular K accumulation during ischemia. However, in addition to these pathways, it seems likely that other pathways for transsarcolemmal K efflux contribute to cellular K loss during ischemia in the isolated rat heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitani
A
A
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
Shattock
M J
MJ
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D003971:Diastole; D005110:Extracellular Space / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology*; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
D002352:Carrier Proteins; D015221:Potassium Channels; D028021:Sodium-Potassium-Chloride Symporters; D010042:Ouabain; D005665:Furosemide; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium