Activation of NMDA receptor-channels in human retinal Müller glial cells inhibits inward-rectifying potassium currents.
Although it is well known that neurotransmitters mediate neuron-to-neuron communication, it is becoming clear that neurotransmitters also affect glial cells. However, knowledge of neuron-to-glial signalling is limited. In this study, we examined the effects of the glutamate agonist N-methyl-D-aspartate (NMDA) on Müller cells, the predominant glia of the retina. Our immunocytochemical studies and immunodetection by Western blotting with monoclonal antibodies specific for the NMDAR1 subunit provided evidence for the expression by human Müller cells of this essential component of NMDA receptor-channels. Under conditions in which potassium currents were blocked, NMDA-induced currents could be detected in perforated-patch recordings from cultured and freshly dissociated human Müller 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, Müller cells remained responsive to NMDA at the resting membrane potential. Under assay conditions not blocking K+ currents, exposure of Müller cells to NMDA was associated with an MK-801 sensitive inhibition of the inward-rectifying K+ current (IK(IR)), the largest current of these glia. This inhibitory effect of NMDA appears to be mediated by an influx of calcium since the inhibition of IK(IR) was significantly reduced when calcium was removed from the bathing solution or when the Müller cells contained the calcium chelator, BAPTA. Inhibition of the Müller cell KIR channels by the neurotransmitter glutamate is likely to have significant functional consequences for the retina since these ion channels are involved in K+ homeostasis, which in turn influences neuronal excitability.
Puro
D G
DG
Department of Ophthalmology, University of Michigan, Ann Arbor 48105, USA.
Yuan
J P
JP
Sucher
N J
NJ
D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology*; D009433:Neural Inhibition; D009457:Neuroglia / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012160:Retina / Q000166:cytology / Q000187:drug effects*
D015221:Potassium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate