The ionic mechanisms concerned in generating the i. p. s. ps of hippocampal pyramidal cells

Abstract A variety of experimental tests has been initiated in order to discover whether the large hyperpolarizing inhibitory postsynaptic potentials (i. p. s. ps) of hippocampal pyramidal cells are generated by the influx of Cl¯ down a gradient maintained by an outward pumping of Cl¯ across the membrane, as has been proposed by Lux, Llinás and associates for other i. p. s. ps. Intravenous infusion of NH4 acetate or intracellular NH4 acetate caused little depression of extracellular field potentials and of i. p. s. ps recorded intracellularly, i. e. there was no evidence for the blockade of an outwardly directed chloride pump. The recovery time constants in seconds from an increase in intracellular chloride, either by chloride injections (22.7 ± 6.9) or by passage of depolarizing current through K+ salt-filled microelectrodes (20.6 + 6.8) did not differ from the time constant of recovery from depleted intracellular chloride by passage of hyperpolarizing current through electrodes containing K+ salts of impermeant anions (21.1 + 5.4). Depletion of the intracellular K+ concentration following sodium injections caused a long-lasting depolarizing shift in the i. p. s. p. with a recovery time constant of almost 70 s. These results are identical with those obtained in spinal moto­neurons, where the very slow recovery was explained by an inward KCl pump triggered by low internal K+. Our results suggest that an outward Cl¯ pump dependent on internal Cl¯ concentration does not exist in hippocampal neurons or at least on their somatic membrane. Two alternative hypotheses are given to account for our negative findings with respect to NH4 acetate action on the hyperpolarizing i. p. s. ps and on the rate of Cl¯ movements across the membrane. First, the original hypothesis as proposed by Eccles and collaborators, in which conductance increases to both Cl¯ and K+ ions produce the hyperpolarizing i. p. s. ps of hippocampal neurons. However, we have no positive evidence for the involvement of K+ ions. Secondly, an outward Cl¯ pump keeps the ECl more negative than the resting potential and the i. p. s. p. is solely caused by Cl¯ as postulated by Lux, Llinás and associates. This pump is located remotely in the dendrites and is resistant to the action of NH4 acetate. This pump would have to be effective in a background manner so that it did not interfere appreciably with the diffusional exchange of Cl¯ ions across the soma membrane.