THROMBIN-INDUCED INHIBITION OF POTASSIUM CURRENTS IN HUMAN RETINAL GLIAL (MULLER) CELLS

1. Glial cells are known to play a role in regulating the microenviron ment of the nervous system. While earlier considerations of glial func tion assumed a passive, static physiology for these cells, this is not likely to be the case. In this study, we begin to examine how the phy siology of Muller glial cells changes in response to molecules in the microenvironment. 2. Perforated-patch recordings and intracellular cal cium measurements were performed on human retinal Muller cells in vitr o. 3. Analysis of whole-cell currents revealed that the human Muller g lial cells have an inwardly rectifying K+ current (I-K(IR)) which is a ctive near the resting membrane potential. This I-K(IR) is significant ly inhibited when the Muller cell is exposed to thrombin, a molecule t hat is likely to enter the retina with a breakdown of the blood-retina l barrier and may be endogenous to the nervous system. 4. A variety of experiments point to a role for Ca2+ as a second messenger mediating the inhibitory effect of thrombin on the I-K(IR) of Muller cells. Spec ifically, thrombin evokes an increase in intracellular [Ca2+] in the M uller cells; the Ca2+ chelator BAPTA blocks the effects of thrombin on both the inhibition of I-K(IR) and the rise in intracellular [Ca2+]; exposure to ionomycin, a calcium ionophore, induces a reduction in the I-K(IR) of Muller cells. 5. A thrombin-induced inhibition in the I-K( IR) of Muller cells is likely to have significant functional consequen ces for the retina since these ion channels are involved in K+ homeost asis. 6. Our experiments support the idea that the physiology of Mulle r glial cells is dynamic and can be markedly affected by molecules in the microenvironment.