Mechanisms for impulse initiation in isolated human atrial fibers.

Abstract

Standard microelectrode techniques were used to study Tyrode''s-superfused human atrial fibers obtained at cardiac surgery. Two types of sustained rhythmic activity occurred. One resulted from slow phase 4 depolarization and had a spontaneous rate, 20-26 beats/min. Epinephrine increased and the slow channel blockers, AHR-2666 (AHR 1-(N-methylcarbamoyl)-3-(m-chlorophenoxy)-pyrrolidine) and verapamil decreased phase 4 slope and spontaneous rate. Acetylcholine (ACh) and lidocaine decreased the slope of phase 4, but the slowing of rate was less than that induced by AHR and verapamil. Tetrodotoxin (TTX) decreased the slope of phase 4 and spontaneous rate to an extent that was intermediate between the actions of AHR-verapamil and ACh-lidocaine. A 2nd type of sustained rhythmic activity was triggered by delayed afterdepolarizations (DAD). DAD amplitude increased as stimulus cycle length decreased and, at critical cycle lengths, DAD initiated trains of spontaneous action potentials at rates > 70 beats/min. Spontaneously occurring DAD were suppressed by AHR and were transiently diminished by ACh. This effect of ACh was accompanied by hyperpolarization of the fibers. DAD were induced by epinephrine. These DAD were unaffected by TTX, lidocaine or ACh and were suppressed by AHR and verapamil. The slow inward current contributes to the sustained rhythmic activity that occurs with automaticity or DAD in human atrium. A TTX-sensitive current contributes to automaticity. DAD that occur spontaneously are largely insensitive to the effects of agents that increase K conductance (although ACh has a transient effect) and those that are induced in the presence of epinephrine do not respond to agents which increase K conductance (ACh, lidocaine) or TTX.