ACTIVATION OF NMDA RECEPTOR-CHANNELS IN HUMAN RETINAL MULLER GLIAL-CELLS INHIBITS INWARD-RECTIFYING POTASSIUM CURRENTS

Although it is well known that neurotransmitters mediate neuron-to-neu ron communication, it is becoming clear that neurotransmitters also af fect glial cells. However, knowledge of neuron-to-glial signalling is limited. In this study, we examined the effects of the glutamate agoni st N-methyl-D-aspartate (NMDA) on Muller cells, the predominant glia o f the retina. Our immunocytochemical studies and immunodetection by We stern blotting with monoclonal antibodies specific for the NMDAR1 subu nit provided evidence for the expression by human Muller cells of this essential component of NMDA receptor-channels, Under conditions in wh ich potassium currents were blocked, NMDA-induced currents could be de tected in perforated-patch recordings from cultured and freshly dissoc iated human Muller cells. These currents were inhibited by competitive and non-competitive blockers of NMDA receptor-channels, Extracellular magnesium reduced the NMDA-activated currents in a voltage-dependent manner. However, despite a partial block by magnesium, Muller cells re mained responsive to NMDA at the resting membrane potential. Under ass ay conditions not blocking K+ currents, exposure of Muller cells to NM DA was associated with an MK-801 sensitive inhibition of the inward-re ctifying K+ current (I-K(IR)), the largest current of these glia. This inhibitory effect of NMDA appears to be mediated by an influx of calc ium since the inhibition of I-K(IR) was significantly reduced when cal cium was removed from the bathing solution or when the Muller cells co ntained the calcium chelator, BAPTA. Inhibition of the Muller cell K-I R channels by the neurotransmitter glutamate is likely to have signifi cant functional consequences for the retina since these ion channels a re involved in K+ homeostasis, which in turn influences neuronal excit ability.