Potentiation by neostigmine of responses to vagal nerve stimulation in thesinus venosus of the toad

The effects of the cholinesterase inhibitor neostigmine on the responses to vagus nerve stimulation of isolated sinus venosus/atrial preparations of t he toad, Bufo marinus, were examined. In control solutions, trains of stimu li applied to the vagus nerve led to a decrease in heart rate that was susc eptible to muscarinic receptor blockade. Membrane potential recordings made from sinus venosus cells showed that the responses to trains of stimuli, d elivered at frequencies of less than 10 Hz, were Little changed by the addi tion of neostigmine. However, the responses to longer trains of stimuli at 10 Hz (30 versus 10 s) were potentiated and the nature of the membrane pote ntial changes was altered. The results suggest that, due to the activity of cholinesterases, acetylcholine (ACh) released from parasympathetic nerves normally has little access to the muscarinic receptors in the pacemaker reg ion, which are linked to potassium channels. (C) 2000 Elsevier Science B.V. All rights reserved.