The Effect of Tetraethylpyrophosphate (TEPP) on the Transmembrane Potentials of Pacemaker and Non-pacemaker Fibers of Isolated Rabbit Atrium

Abstract
When 7 x 10-7M tetraethylpyrophosphate (TEPP) was administered as constant perfusion, the results were: (1) A progressive slowing of atrial rate and subsequent block in conduction; (2) A decrease in slope of the prepotential of pacemaker fibers; (3) No significant change in membrane resting potential of sinoatrial and atrial fibers, even during block in conduction; (4) An accelerated repolarization of both types of fibers. Simultaneously with the changes in electrical activity TEPP consistently produced a progressive decrease in inotropism. Pyridine 2-aldoxime methiodide (PAM) in concentrations of 1.26-2.52 x 10-4M consistently reversed the effects of TEPP. The inotropism often exceeded the control. The data suggests that 1) the changes in transmembrane potential produced by TEPP are principally due to an acetylcholine action, 2) the decrease in contractility is more intimately related to a disturbance in metabolic energy, and 3) the reversibility of the TEPP effects by PAM is due to a reactivation of acetylcholinesterase, an action similar to that observed in vitro.