Abstract
P 075
Volume regulation of Müller cells: Involvement of voltage-gated calcium and sodium channels
Regina Linnertz1, Andreas Bringmann2, Peter Wiedemann2, Andreas Reichenbach1
1Paul-Flechsig-Institut für Hirnforschung, Fakultät für Medizin, Universität Leipzig, Leipzig; 2Klinik und Poliklinik für Augenheilkunde, Medizinische Fakultät der Universität Leipzig, Leipzig
Objective
One important function of Müller cells is the maintenance of the volume homeostasis of the retinal tissue. Swelling of Müller cells was suggested to be involved in development of retinal edema. Hypoosmotic conditions in the presence of inflammatory mediators or under oxidative stress, and during blockade of potassium channels, induce swelling of Müller cells. The aim of our study was to determine whether receptor agonists which evoke a calcium response in Müller cells may prevent the osmotic swelling of Müller cells. In further experiments we investigated the involvement of voltage-gated sodium and calcium channels in the autocrine regulation of Müller cell volume.
Methods
Freshly isolated Müller cells of the rat were perfused with isotonic or hypotonic solution. To determine the volume changes of the cells the cross sectional area of the somata was measured with a laser scanning microscope.
Results
We found that vascular endothelial growth factor, heparin-binding EGF-like growth factor, neuropeptide Y, atrial natriuretic peptide and erythropoietin prevented the osmotic swelling of the cells. Activation of specific receptors evoked a calcium-dependent, exocytotic release of glutamate from Müller cells, and subsequent stimulation of glial group I/II metabotropic glutamate receptors. Activation of glutamate receptors evoked an autocrine swelling-inhibitory purinergic signalling cascade that was calcium-independent. We found that the inhibitory effect of the agonists on the osmotic swelling of retinal glial cells was prevented in the presence of inhibitors of voltage-gated sodium (tetrodotoxin) and T-type calcium channels (kurtoxin). In contrast, the swelling-inhibitory effect of glutamate remained unaffected in the presence of the blockers.
Conclusions
The present results indicate a functional role of voltage-dependent calcium channels in the mediation of the calcium influx for the vesicular release of glutamate from Müller cells. The involvement of voltage-dependent sodium channels suggests that rapid fluctuations of the membrane potential underlie the activation of calcium channels.
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