Inhibitory effect of 9-amino-1,2,3,4-tetrahydroacridine (THA) on the potassium current of rabbit sinoatrial node.
STUDY OBJECTIVE - To examine the effect of 9-amino-1,2,3,4-tetrahydroacridine (THA), a compound similar to the K+ blocker 4-aminopyridine, on potassium channels in the sinoatrial node. DESIGN - The pacemaking portion of rabbit sinoatrial nodes was studied using the double microelectrode voltage clamp method in the presence of THA at various concentrations. MEASUREMENTS AND RESULTS - Above 1 mumol.litre-1, THA prolonged the spontaneous cycle length and the transmembrane action potential duration at 50% repolarisation. Above 10 mumol.litre-1, the compound also decreased the maximum rate of rise, the action potential amplitude, and the rate of diastolic depolarisation. Under voltage clamp conditions, THA reduced the time dependent K+ current (IK) in a dose dependent manner. Neither the decay process of IK nor its activation process were altered by THA. CONCLUSIONS - THA depresses sinoatrial node IK without changing its kinetics. Thus it may inhibit the open state of the potassium channels.
Kotake
H
H
1st Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Hisatome
I
I
Matsuoka
S
S
Miyakoda
H
H
Hasegawa
J
J
Mashiba
H
H
D000544:Alzheimer Disease / Q000188:drug therapy; D000609:Aminoacridines / Q000494:pharmacology*; D000818:Animals; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects*; D013619:Tacrine / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D000609:Aminoacridines; D015221:Potassium Channels; D013619:Tacrine; D014700:Verapamil