a1 Departments of Ophthalmology and Physiology, University of Michigan, Ann Arbor
a2 Department of Neurology, Children's Hospital, Harvard Medical School, Boston
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.
(Received June 19 1995)
(Accepted August 17 1995)
Reprint requests to: Donald G. Puro, W.K. Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA.