L-METHIONINE AS A MODULATOR OF ATRIAL RHYTHMICITY IN RABBIT AND GUINEA-PIG

Abstract

By using the intracellular microelectrode technique, Toda (1) reported the effects of adrenaline, noradrenaline and reserpine on transmembrane potentials in pacemaker and non-pacemaker fibers of isolated rabbit atria, and suggested that endogenously liberated adrenaline and noradrenaline play an important physiological role in initiating and maintaining atrial rhythmicity. Further studies on cardiac mechanism were done by Matsuo and Tachi (2) who suggested that the initiating substance in atrial contraction may be adrenaline or noradrenaline in isolated atrial preparation. On the other hand, Bulbring and Burn (3, 4) concluded that the local formation of acetylcholine initiates auricular contraction. Kottegoda (5) also reported that acetylcholine in a high concentrations had a stimulant action on rabbit atria in the presence of atropine. In rabbit auricles, noradrenaline and acetylcholine were found present in about the same amounts of 1.3 to 1.48 μg/g [Burn (4), Matsuo (6)]. From these observations it may safely be assumed that endogenous acetylcholine is the trigger substance in the release of endogenous adrenaline or noradrenaline which, in turn, initiates atrial movement. Conversely, the depletion of endogenous acetylcholine or noradrenaline in atria may cause the arrest of atrial movement. Paasonen and Krayer (7) have shown that the administration of reserpine to a dog heart-lung preparation leads to a marked decrease in the noradrenaline content of the heart, but the adrenaline content normally 5 per cent that of noradrenaline shows no clear-cut decrease. This result would indicate that, rather than noradrenaline, endogenous adrenaline may be the more important hormone relative to atrial movement. Kirshner and Goodall (8) have shown that the soluble fraction of adrenal medullary hon ogenates form adrenaline from noradrenaline and L-methionine in the presence of ATP. Pilgeram et al. (9) suggested that the methyl groups of choline may be derived by transmethylation from L-methionine, and that the active formation of phospholipid choline from aminoethanol was obtained only through utilization of the methyl group of L-methionine. It may therefore be assumed that L-methionine is the substance essential both to endogenous adrenaline and acetylchholine, which are the initiators and modulators of atrial rhythmicity. The present experiment was carried out to study the effects of L-methionine on isolated normal, or reserpine or nicotine-treated atria, in order to discover the physiological role of L-methionine in the cardiac mechanism.