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

Abstract

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.

Propagation velocity of epileptiform activity in the hippocampus

“…Thus, the velocity of ephaptic propagation will increase at an increased K + concentration. In contrast, the conduction velocity of nerve fibres may decrease (Poolos et al 1987).…”

“…However, these velocities may differ somewhat in the epileptogenic slice where the extracellular K § concentration is increased (Heinemann et al 1977;Somjen and Giacchino 1985;Heinemann 1987). Poolos et al (1987) reported a decrease in propagation velocity of fibres in the stratum radiatum of CA1 by~ 30% at an increase of the interstitial K § concentration from 3 to 9 mM. If there is any effect of extracellular K § on the propagation velocity of fibres in the epileptogenic slice, it will be a decrease.…”

Dual Electrophysiological Recordings of Synaptically-evoked Astroglial and Neuronal Responses in Acute Hippocampal Slices

“…The synaptically-evoked glial membrane depolarization is a direct measure of the extracellular potassium rise 8 , due in part to presynaptic action potential firing, but mostly to postsynaptic depolarization 7 . Therefore recordings of glial membrane potential dynamics can be used to investigate modifications in presynaptic excitability, postsynaptic activity, extracellular space volume and potassium buffering capacities 6,8 .…”

“…To visualize the extent of the gap-junction mediated astroglial networks, dye-coupling experiments should be performed in current clamp mode, without any current injection, to enable passive diffusion of low molecular dyes (< 1.5 kDa), such as sulforhodamine-B, through gap . The majority of the slow inward current reflects potassium entry into the astrocyte following postsynaptic depolarization, since it is also abolished by kynurenic acid, which inhibits postsynaptic ionotropic glutamate receptor activity ( Figure 2B and Figure 2C 1 ) [3][4][5][6] , known to represent the main source (80 %) of potassium release 7 . The remaining rapidly rising and decaying inward current is inhibited by the GLT antagonist DL-TBOA (light grey trace, Figure 2B and Figure 2C 2 ).…”

Information processing in the axon

“…The Na + /K + pump is activated and the concentration of extracellular potassium decreases at a greater rate around the thin branch 82 . Accumulation of extracellular potassium has also been observed in the olfactory nerve 90 and in hippocampal axons 91 , and could be the origin of unreliable conduction. Propagation failures that are induced by repetitive stimulation might also result from hyperpolarization of OUABAIN Extracted from the seed of the Strophantus, a tropical creeper, ouabain is a cardiotonic that blocks sodium channel electrogenic pumps.…”