The excitatory action of acetylcholine on hippocampal neurones of the guinea pig and rat maintained in vitro

Abstract

In preliminary experiments on 39 identified pyramidal cells in the in vitro slice preparation of the guinea-pig hippocampus the depolarization evoked by acetylcholine (ACh) applied by microiontophoresis was always associated with an increase in membrane resistance. In 9 slices cut from the rat hippocampus similar results were obtained from 24 cells. In a more detailed analysis on 13 cells from the rat hippocampus, whose mean resting potential was — 74 mV and mean resting input resistance 33 Mω, the mean peak depolarization evoked by ACh was 11.6 mV and the mean increase in membrane resistance 12 Mω. The reversal potential for the excitatory action of ACh was 29 mV more hyperpolarizing than the resting membrane potential. The depolarization evoked by ACh was linearly related to the corresponding increase in membrane before and after the application of ACh. This was true throughout each of the individual applications of ACh and of the peak response evoked by each of the 13 applications. The constancy of this relationship is compatible with the usual model used to describe synaptic events thought to be mediated by the closure of ionic channels which are open in the absence of the transmitter. The onset of the response to ACh was always approximately 4 times slower than that evoked by a near equipotent microiontophoretic application of glutamate from an adjacent barrel of the same multibarrelled micropipette. Following the application of ACh, recovery was also slow and, on average, was approximately 10 times longer than that following a near equipotent application of glutamate. It is suggested that the slow onset and offset of the responses evoked by ACh are not compatible with models based on diffusion and are best explained by postulating a sequential generation of one or more intermediates.