Abstracts

RATIONALE: HERG (human ether-a-go-go) potassium channels are activated by depolarization and show large tail currents that contribute to the apparent inward-going rectification of whole cell currents. In our previous studies of CNS glia in hippocampal slices, we found that HERG channels are selectively localized in astrocytes. Electrophysiological characterization of HERG channels suggested that these channels contribute to the modulation of extracellular potassium levels following neuronal activation. We now report in vivo electrophysiological data that indicate that HERG channel are indeed involved in the regulation of the neuronal excitability. METHODS: In vivo recordings of hippocampal activity were performed in anaesthetized (urethane, 1.5 gr/Kg) male Wistar rats. A stimulating electrode was implanted in CA3. E4031, a HERG blocker, was administered (concentration of 4, 6, or 8 ?g in 2 ?l of ACSF) into hippocampus via a cannula implanted in CA1. An electrode placed in CA1, near the site of injection, was used to record CA3-evoked field potentials before, during, and after the injection of drug. A control group of rats was prepared and injected with vehicle (ACSF). RESULTS: Injection of 4 ?g/2 ?l of E4031 resulted in no effects on field potentials, similarly to the injection of ACSF alone. In contrast, injection of 6 ?g/2 ?l of E4031 caused a significant and long-lasting (over 1 hour) increase in field potential magnitude (fEPSP rate of rise and population spike amplitude (n = 3, p<0.05 and n = 3, p<0.06, respectively). Finally, administration of 8 ?g/2 ?l showed a transient (5-10 min) decrease in field amplitude followed by a long- lasting increase of the field potentials. CONCLUSIONS: Our results support the view that HERG channels contribute to the regulation of neuronal activation, presumably by their regulation of potassium homeostasis. Since HERG channels are specific to glia, these data provide additional evidence for the critical role played by glia in controlling excitability and therefore epileptogenicity of the neuronal population. Supported by an AES/EF fellowship and NIH, NS 35548