Characterization of recombinant human cardiac KCNQ1/KCNE1 channels (I (Ks)) stably expressed in HEK 293 cells

J Membr Biol. 2006 Apr;210(3):183-92. doi: 10.1007/s00232-006-0006-5. Epub 2006 Aug 14.


The present study was designed to characterize pharmacological, biophysical and electrophysiological properties of the recombinant human cardiac I (Ks) (KCNQ1/KCNE1) channels at physiological temperature. Human cardiac KCNQ1 and KCNE1 genes were cotransfected into HEK 293 cells, and a cell clone stably expressing both genes was selected. Membrane currents were recorded using a perforated patch-clamp technique. The typical I (Ks) was slowly activated upon depolarization voltages in HEK 293 cells stably expressing human cardiac KCNQ1 and KCNE1 genes, and the current was inhibited by I (Ks) blockers HMR 1556 and chromanol 293B, with 50% inhibitory concentrations (IC(50)s) of 83.8 nM: and 9.2 muM: , respectively. I (Ks) showed a significant temperature-dependent increase in its magnitude upon elevating bath temperature to 36 degrees C from room temperature (21 degrees C). The current was upregulated by the beta-adrenoceptor agonist isoproterenol, and the effect was reversed by H89. In addition, I (Ks) was inhibited by Ba(2+) in a concentration-dependent manner (IC(50) = 1.4 mM). Action potential clamp revealed a "bell-shaped" time course of I (Ks) during the action potential, and maximal peak current was seen at the plateau of the action potential. A significant use- and frequency-dependent increase of I (Ks) was observed during a train of action potential clamp. These results indicate that the recombinant human cardiac I (Ks) stably expressed in HEK 293 cells is similar to native I (Ks) in drug sensitivity and regulated by Ba(2+) and beta-adrenoceptor via the cyclic adenosine monophosphate/protein kinase A pathway. Importantly, the current exhibits significant temperature dependence, a bell-shaped time course during action potential and prominent use- or frequency-dependent accumulation during a train of action potentials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Adrenergic beta-Agonists / pharmacology
  • Barium / pharmacology
  • Cells, Cultured
  • Chromans / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Gene Expression Regulation / physiology*
  • Humans
  • Isoproterenol / pharmacology
  • Isoquinolines / pharmacology
  • KCNQ1 Potassium Channel / antagonists & inhibitors
  • KCNQ1 Potassium Channel / physiology*
  • Kidney / embryology
  • Kidney / metabolism*
  • Membrane Potentials / drug effects
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors
  • Potassium Channels, Voltage-Gated / physiology*
  • Protein Kinase Inhibitors / pharmacology
  • Recombinant Proteins / metabolism
  • Sulfonamides / pharmacology
  • Transfection


  • Adrenergic beta-Agonists
  • Chromans
  • HMR 1556
  • Isoquinolines
  • KCNE1 protein, human
  • KCNQ1 Potassium Channel
  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • Protein Kinase Inhibitors
  • Recombinant Proteins
  • Sulfonamides
  • 6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane
  • Barium
  • Cyclic AMP-Dependent Protein Kinases
  • Isoproterenol
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide