Inhibitory effect of 9-amino- 1,2,3,4-tetrahydroacridine (THA) on the potassium current of rabbit sinoatrial node

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Abstract
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 pace making 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 μmol·litre−1, THA prolonged the spontaneous cycle length and the transmembrane action potential duration at 50% repolarisation. Above 10 μmol·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.