FACILITATORY DRUG ACTION ON THE ISOLATED PHRENIC NERVE-DIAPHRAGM PREPARATION OF THE RAT

¹ Australian Defence Scientific Service, Defence Standards Laboratories, Maribyrnong, Australia

The action of facilitatory drugs was studied in the phrenic nerve-diaphragm preparation and the chronically denervated diaphragm of the rat. The latter was used as a model of the postsynaptic receptor. The drugs were tetrahydro-4-aminoacridine and a series of hydroxyanilinium compounds which included edrophonium. The drugs caused twitch potentiation and spontaneous activity in the intact preparation; these effects were depressed by temperature reduction, low Ca⁺⁺ solutions or high Mg⁺⁺ solutions. The acetylcholine contraction of the denervated diaphragm was potentiated by all drugs except 3-hydroxyphenyltriethylammonium. The acetylcholine depolarization was similarly affected. This potentiation was suppressed by raised levels of Ca⁺⁺ or Mg⁺⁺. Interactions between the facilitatory drugs and succinylcholine are described. Succinylcholine abolished twitch potentiation of the intact preparation at low concentrations; only 3-hydroxyphenyldiethylmethylammonium proved to be an effective antagonist of succinylcholine blockade. Facilitation in the intact junction appears to be largely a presynaptic effect.