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Therapeutic potential of modulating potassium currents in the diseased myocardium 1
Author(s) -
Lynch Joseph J.,
Sanguinetti Michael C.,
Kimura Shinichi,
Bassett Arthur L.
Publication year - 1992
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.6.11.1386585
Subject(s) - potassium channel , refractory period , cardiology , medicine , inward rectifier potassium ion channel , potassium channel blocker , pharmacology , effective refractory period , anti arrhythmia agents , atrial fibrillation , ion channel , receptor
Myocardial disease states are characterized by multiple electrophysiologic abnormalities, including alterations in potassium channel activities. During acute myocardial ischemia, activation of ATP‐regulated K + current (I K( atp ) ) results in shortening of action potential duration and elevation of extracellular K + concentration. In hypertrophied myocardium, increases in inward rectifier K + current (I K1 ) and decreases in delayed rectifier K + current (I K ) are observed. Alterations in K + channel activity in myocardial disease states suggest the potential to therapeutically modify cardiac rhythm and function with K + channel modulators. Glass III antiarrhythmic agents, which prolong myocardial refractoriness predominantly via a blockade of I K , have demonstrated efficacy in suppressing reentrant atrial and ventricular arrhythmias in animal models as well as promising efficacy in initial clinical studies. Potassium channel openers (PCOs), which activate cardiac I K(ATP) , have demonstrated both antiarrhythmic and proarrhythmic activities in various experimental settings, and also are being investigated as potential cardioprotective agents. Sulfonylureas, which block cardiac I k (ATP) , also have been investigated as potential antiarrhythmic agents with equivocal results, and have displayed a propensity to exacerbate ischemic myocardial dysfunction in experimental studies. A more comprehensive understanding of K + channel activity in various myocardial disease states, including concomitant disorders such as myocardial ischemia and hypertrophy, will facilitate the development of more useful potassium channel modulators, as well as a clearer recognition of the undesirable effects of such agents.— Lynch, J. J.; Sanguinetti, M. C.; Kimura, S.; Bassett, A. L. Therapeutic potential of modulating potassium currents in the diseased myocardium. FASEB J. 6: 2952‐2960; 1992.