Stimulation of phrenic nerve activity by an acetylcholine releasing drug: 4-aminopyridine.

The effect of the acetylcholine releaser 4-aminopyridine on ventilation was studied by recording and quantifying the efferent phrenic nerve activity in 40 paralysed and vagotomized cats; with arterial Po2, PCO2 and pH kept constant. 4-Aminopyridine, given intravenously or in the vertebral artery, stimulates the phrenic nerve activity in a dose dependent manner. The stimulatory effects of 4-aminopyridine on the phrenic nerve activity could be abolished completely by administration of high doses of atropine. We conclude that 4-aminopyridine, which is used clinically for the reversal of a neuromuscular block, stimulates the phrenic nerve activity. Since the role of cholinergic mechanisms in the central chemoreception has been well established, the effect on the phrenic nerve activity is most probably by an increased release of acetylcholine at the site of the central chemoreceptors.