Evidence for Two Components of Delayed Rectifier K+ Current in Human Ventricular Myocytes

摘要: Abstract Previous voltage-clamp studies have suggested that the delayed rectifier current (IK) is small or absent in human ventricle and, when present, consists only of rapid component (IKr); however, molecular suggest presence functionally important IK heart, specific IKr blockers are known to delay ventricular repolarization and cause long QT syndrome humans, we shown expression strongly influenced by cell isolation techniques. The present experiments were designed assess myocytes obtained arterial perfusion right tissue from explanted hearts. Of 35 cells three hearts, 33 (94%) showed time-dependent currents typical IK. envelope-of-tails test was not satisfied under control conditions but became benzenesulfonamide E-4031 (5 μmol/L). suppressed a portion 32 cells, with properties drug-sensitive -resistant components consistent previous descriptions slow (IKs), respectively. Action potential duration 95% at 1 Hz prolonged 336±16 (mean±SEM) 421±19 ms (n=5, P <.01), indicating functional role for Indapamide, diuretic agent previously inhibit IKs selectively, E-4031–resistant current. third type rectifier, ultrarapid (IKur), evaluated use depolarizing prepulses low concentrations (50 μmol/L) 4-aminopyridine. Although these techniques revealed clear IKur five atrial no corresponding observed any myocytes. We conclude significant IK, IKs, whereas appears be absent. These findings understanding molecular, physiological, pharmacological determinants arrhythmias.