Role of rapidly activating delayed rectifier K+ current in sinoatrial node pacemaker activity.
A rapidly activating component of delayed rectifier K+ current (IK,r) was dissected using a selective blocker, E-4031, during the action potential clamp (AP clamp) in rabbit sinoatrial node cells. Application of E-4031 induced a large compensation current, of which amplitude was similar to or larger than the net current during repolarization and was maximum (2.2 +/- 0.2 pA/pF) at -46.0 +/- 1.8 mV (n = 13). During the slow diastolic depolarization, the compensation current gradually decayed and then abruptly decreased at the peak of action potential. The time-dependent change of IK,r was calculated using a mathematical model, in which independent gates of activation and inactivation were assumed based on the whole cell voltage-clamp experiments. The reconstructed IK,r corresponded well with the E-4031-sensitive current measured by the AP clamp method. Partial block of IK,r by E-4031 in spontaneously beating cells decreased the action potential amplitude, maximum rate of rise, and maximum rate of repolarization and induced a positive shift of the maximum diastolic potential. Complete block of IK,r terminated the spontaneous action potential at -37.4 +/- 2.9 mV (n = 3). It is concluded that IK,r plays an essential role in determining the maximum diastolic potential and ensures the firing of the following action potential in sinoatrial node cells.
Ono
K
K
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ito
H
H
D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D003198:Computer Simulation; D004594:Electrophysiology; D006339:Heart Rate / Q000502:physiology*; D007700:Kinetics; D008955:Models, Cardiovascular; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D015221:Potassium Channels; D011725:Pyridines; C063968:E 4031