Two components of the delayed rectifier potassium current, IK, in rabbit sino-atrial node cells.
The delayed rectifier current was studied in rabbit isolated sino-atrial (SA) node cells using the whole-cell voltage clamp technique with amphotericin-permeabilized patches. The envelope of tails test indicated that in SA node cells the decay of IK (IK.tall) comprises two distinct current components similar to the specific fast and slow components of IK (IKr and JKs) that have been found in atrial and ventricular myocytes. Dofetilide, a Class III antiarrhythmic agent and a selective blocker of IKr. separated the delayed rectifier current into drug-sensitive current (IKr) and drug-insensitive current (IKs). The dofetilide-sensitive current activated rapidly and it showed two components of deactivation, the larger of which was very slow, while the dofetilide-insensitive current activated more slowly and deactivated quickly. The effects of propofol, an IKs blocker, on the delayed rectifier current were also investigated. The results show that IKs contributes to IK.tall and that the more positive the membrane potential, the more the contribution of IKs. The ratio of IKs to IKr in tail currents at -40 mV after a 1 s clamp pulse to +40 mV was 0.3-0.4:1. Dofetilide slowed spontaneous activity, suggesting that IKr contributes to the pacemaker activity of the SA node cell.
University Laboratory of Physiology, Oxford, UK.
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M
Lei
H F
HF
Brown
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials; D010627:Phenethylamines / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D015742:Propofol / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D051668:Delayed Rectifier Potassium Channels; D006993:Hypnotics and Sedatives; D010627:Phenethylamines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; C063533:dofetilide; D015742:Propofol