Do glia have heart? Expression and functional role for ether-a-go-go currents in hippocampal astrocytes

Potassium homeostasis plays an important role in the control of neuronal ex citability, and diminished buffering of extracellular K results in neuronal Hyperexcitability and abnormal synchronization. Astrocytes are the cellula r elements primarily involved in this process. Potassium uptake into astroc ytes occurs, at least in part, through voltage-dependent channels, but the exact mechanisms involved are not fully understood. Although most glial rec ordings reveal expression of inward rectifier currents (K-IR), it is not cl ear how spatial buffering consisting of accumulation and release of potassi um may be mediated by exclusively inward potassium fluxes. We hypothesized that a combination of inward and outward rectifiers cooperate in the proces s of spatial buffering. Given the pharmacological properties of potassium h omeostasis (sensitivity to Cs+), members of the ether-a-go-go (ERG) channel family widely expressed in the nervous system could underlie part of the p rocess. We used electrophysiological recordings and pharmacological manipul ations to demonstrate the expression of ERG-type currents in cultured and i n situ hippocampal astrocytes. Specific ERG blockers (dofetilide and E 4031 ) inhibited hyperpolarization- and depolarization-activated glial currents, and ERG blockade impaired clearance of extracellular potassium with little direct effect on hippocampal neuron excitability. Immunocytochemical analy sis revealed ERG protein mostly confined to astrocytes; ERG immunoreactivit y was absent in presynaptic and postsynaptic elements, but pronounced in gl ia surrounding the synaptic cleft. Oligodendroglia did not reveal ERG immun oreactivity. Intense immunoreactivity was also found in perivascular astroc ytic end feet at the blood-brain barrier. cDNA amplification showed that co rtical astrocytes selectively express HERG1, but not HERG2-3 genes. This st udy provides insight into a possible physiological role of hippocampal ERG channels and links activation of ERG to control of potassium homeostasis.