THE MULLER (GLIAL) CELL IN NORMAL AND DISEASED RETINA - A CASE FOR SINGLE-CELL ELECTROPHYSIOLOGY

In the retina of most vertebrates there exists only one type of macrog lia, the Muller cell. Muller cells express voltage-gated ion channels, neurotransmitter receptors and various uptake carrier systems. These properties enable the Muller cells to control the activity of retinal neurons by regulating the extracellular concentration of neuroactive s ubstances such as K+, GABA and glutamate. We show here how electrophys iological recordings from enzymatically dissociated mammalian Muller c alls can be used to study these mechanisms. Muller cells from various species have Na+-dependent GABA uptake carriers, but only cells from p rimates have additional GABA receptors that activate Cl- channels. App lication of glutamate analogues causes enhanced membrane currents reco rded from Muller cells in situ but not from isolated cells. We show th at mammalian Muller cells have no ionotropic glutamate receptors but r espond to increased K+ release from glutamate-stimulated retinal neuro ns, This response is involved in extracellular K+ clearance and is med iated by voltage-gated (inwardly rectifying) K+ channels which are abu ndantly expressed by healthy Muller cells, In various cases of human r etinal pathology, currents through these channels are strongly reduced or even extinguished, Another type of voltage-gated ion channels, obs erved in Muller cells from many mammalian species, are Na+ channels. I n Muller cells from diseased human retinae, voltage-dependent Na+ curr ents were significantly increased in comparison to cells from control donors, Thus, the expression of glial ion channels seems to be control led by neuronal signals. This interaction may be involved in the patho genesis of retinal gliosis which inevitably accompanies any degenerati on of retinal neurons. In particular. Muller cell proliferation may be triggered by mechanisms requiring the activation of Ca2+-dependent K channels, Ca2+-dependent K+ currents are easily elicitable in Muller cells from degenerating retinae and can be blocked by I atl TEA (tetra ethylammonium). In purified Muller cell cultures, the application of 1 mM TEA greatly reduces the proliferative activity of the cells. These data clearly show that Muller cells are altered in cases of neuronal degeneration and may be crucially involved in pathogenetic mechanisms of the retina.