Epileptiform discharges induced by altering extracellular potassium and calcium in the rat hippocampal slice

Abstract

During and after intense neuronal activity the concentration of extracellular potassium ([K +] 0) increases while the concentration of calcium ([Ca 2+] 0) decreases. The present study examined the effect of increased [K +] 0 alone, and with a parallel decrease in [Ca 2+] 0, on overall excitability, long-term potentiation (LTP), and the appearance of epileptiform discharges. [K +] 0 and [Ca 2+] 0 were varied over the range in which they fluctuate in vivo. Hippocampal slices were first equilibrated in a control artificial CSF containing 3.1 m M K + and 1.5 m M Ca 2+ and then reequilibrated in an identical solution except that the K + was increased to 3.55, 4, 5, 6, or 8 m M with and without a decrease in Ca 2+ to 1.0 m M. Raising [K +] 0 caused a leftward shift of input-output curves. Lowering [Ca 2+] 0 to 1.0 m M had no effect on the ability of [K +] 0 to shift the input-output curve to the left. LTP was not changed by increasing [K +] 0. Lowering [Ca 2+] 0 to 1.0 m M blocked LTP and increasing the [K +] 0 did not overcome this blockade. When [K +] 0 alone was altered, the [K +] 0s at which epileptiform bursts occurred 50% of the time were 5.6 and 7.6 m M for stimulus-locked and spontaneous bursting, respectively. The combination of decreased [Ca 2+] 0 and increased [K +] 0 made slices considerably more prone to epileptiform activity. In 1.0 m M [Ca 2+] 0, the [K +] 0 at which 50% of the slices showed stimulus-locked bursting was decreased to 3.6 m M while that for spontaneous discharges was 5.4 m M. The sensitivity of hippocampal slices to [K +] 0 and [Ca 2+] 0, and the synergistic actions of alterations of these ions, indicates that even small changes in the aggregate extracellular ionic milieu may be important in epileptogenesis.