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  Interaction of calcium-permeable non-N-methyl-d-aspartate receptor channels with voltage-activated potassium and calcium currents in rat retinal ganglion cells in vitro

Taschenberger, H., & Grantyn, R. (1998). Interaction of calcium-permeable non-N-methyl-d-aspartate receptor channels with voltage-activated potassium and calcium currents in rat retinal ganglion cells in vitro. Neuroscience, 84(3), 877-896. doi:10.1016/S0306-4522(97)00541-1.

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Taschenberger, Holger1, Author                 
Grantyn, R., Author
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 Abstract: Calcium-permeable non-N-methyl-d-aspartate receptor channels are now characterized in much detail, but still little is known about the consequences of Ca2+ influx through these channels in specific neuron types. We are interested in the role of Ca2+-permeable non-N-methyl-d-aspartate receptor channels during differentiation of retinal ganglion cells. However, in view of the conflicting data on the relative Ca2+ permeability of non-N-methyl-d-aspartate receptor channels in these neurons, a more systematic evaluation of permeation properties of different Na+ substitutes was necessary before proceeding with the main goal of the present study—evaluating the effects of non-N-methyl-d-aspartate receptor activation on repetitive firing and voltage-activated K+ and Ca2+ conductances. Retinal ganglion cells were dissociated from the rat retina on postnatal day 5. They were selected by vital anti-Thy-1 immunostaining and repetitive firing behaviour and submitted to patch-clamp recording in the whole-cell configuration. Non-N-methyl-d-aspartate receptor channels were activated by application of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainate. It was found that they were essentially impermeable to N-methyl-d-glucamine (PNMDG/PCs<0.02), but not to choline (Pcholine/PCs=0.24) and tetramethylammonium (PTMA/PCs=0.23). When using N-methyl-d-glucamine as a substitute for Na+ to obtain bi-ionic conditions PCa/PCs varied between 0.08 to 1.40. Linear current-voltage relation or little outward rectification corresponded to a low Ca2+ permeability (PCa/PCs=0.14). In about one third of the cells kainate-induced currents showed inward rectification and non-N-methyl-d-aspartate receptor agonists induced a substantially higher Ca2+ influx (PCa/PCs=0.64). Activation of non-N-methyl-d-aspartate receptors by kainate profoundly altered the repetitive discharge of retinal ganglion cells. In contrast to the continuously firing controls, cells generated only a few spikes at the beginning of a steady depolarization after kainate exposure. Among the candidates regulating the firing behaviour of retinal ganglion cells voltage-activated Ca2+ and K+ conductances were tested for their sensitivity to kainate application. It was found that even short conditioning pulses of kainate decreased the peak amplitudes of both voltage-activated K+ and voltage-activated Ca2+ currents. Only the latter effect required extracellular Ca2+ and was antagonized by increasing the intracellular Ca2+ buffering strength. Thus, suppression of calcium currents was induced by a non-N-methyl-d-aspartate receptor-mediated rise of the intracellular calcium concentration. The reduction of K+ currents did not depend on extracellular calcium and was insensitive to experimental manipulation of intracellular Ca2+ buffer strength.





The interaction between Ca2+-permeable non-N-methyl-d-aspartate receptor channels and voltage-activated Ca2+ and K+ currents may represent an important regulatory mechanism to control the repetitive firing of developing retinal ganglion cells.

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Language(s): eng - English
 Dates: 1998
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1016/S0306-4522(97)00541-1
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Title: Neuroscience
Source Genre: Journal
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Publ. Info: Amsterdam : Elsevier
Pages: - Volume / Issue: 84 (3) Sequence Number: - Start / End Page: 877 - 896 Identifier: ISSN: 0306-4522
CoNE: https://pure.mpg.de/cone/journals/resource/954925514498