Activity-evoked increases in extracellular potassium modulate presynaptic excitability in the CA1 region of the hippocampus.

1. The effects of stimulus-evoked potassium release on the excitability of presynaptic axons were studied in the rat hippocampal slice preparation. Extracellular stimulation and recording in the stratum radiatum of CA1 yielded a characteristic field potential corresponding to the compound action potential of nonmyelinated afferents and subsequent postsynaptic activation of pyramidal cells. 2. Repetitive stimulation (1 s; 2-100 Hz) produced biphasic changes in the excitability of the afferents. Initial responses showed increased conduction velocity and variably increased amplitude; subsequent responses showed progressively decreasing conduction velocity and amplitude tending toward conduction block. Decreases in excitability were maximal at the end of stimulation and were more pronounced with higher stimulation frequencies. 3. When synaptic transmission was abolished with superfusate containing elevated [Mg2+] (6 mM) and decreased [Ca2+] (0.25 mM), kynurenic acid (1 mM), or adenosine (100 microM), the ability of the fibers to follow repetitive stimulation was enhanced, as indicated by a reduction in amplitude decrement of the presynaptic volley. The decrease in conduction velocity at the end of stimulation was less than half that obtained with intact postsynaptic activity. 4. Concomitant with changes in the excitability of CA1 afferents, the concentration of extracellular potassium ( [K+]o) increased up to 7 mM, as recorded in the stratum radiatum with potassium ion-sensitive microelectrodes. When postsynaptic activity was blocked, activity-evoked rises in [K+]o were reduced to less than 25% of their former value. This suggests that activity-evoked increases in [K+]o derive predominantly from postsynaptic elements. 5. Superfusion of solutions containing elevated [K+] produced biphasic changes in the excitability of CA1 afferents that were qualitatively similar to those produced by repetitive stimulation. Elevated [K+]o below 6 mM produced increased excitability, whereas [K+]o above 6 mM yielded decreased excitability. 6. These results demonstrate that in the CA1 region of the hippocampus, significant rises in [K+]o occur with activity and derive predominantly from postsynaptic elements. The conduction properties of CA1 afferents are sensitive to the level of [K+]o, whether altered artificially or by activity. These effects may constitute a mechanism of postsynaptic modulation of presynaptic conduction operating within a broad range of afferent firing frequencies in the hippocampus.