Serum-induced changes in the physiology of mammalian retinal glial cells: role of lysophosphatidic acid.

1. With a breakdown of the vascular-CNS barrier, serum enters the nervous system. Although this is a frequent pathophysiological event, knowledge of the effects of serum on the function of the nervous system is limited. In this study, we examined the effects of serum on the activity of ion channels in Müller cells: the principal glia of the retina. 2. Freshly dissociated Müller cells from the bovine and human retina were studied with the perforated-patch configuration of the patch clamp technique. In other experiments, electroretinograms (ERGs) were recorded from isolated rat retinas. 3. Perforated-patch recordings revealed that serum induced a calcium-permeable, non-specific cation (NSC) current. Approximately 40 s after induction of this current, an outwardly rectifying K+ current was also detected. Sensitivity to charybdotoxin and margatoxin indicated that this K+ current was due to the activation of Kv1.3 channels. This increase in the Kv1.3 current was dependent on extracellular calcium. 4. The NSC and Kv1.3 currents were activated by serum in 100% and 95% of the sampled Müller cells, respectively. Also, in a minority (21%) of the cells, the inwardly rectifying K+ current was inhibited slightly. These changes in ion channel activity were associated with depolarization of the Müller cells. 5. We hypothesized that activation of NSC channels would reduce the siphoning of K+ via the Müller cells. Consistent with this idea, ERGs from isolated retinas showed serum-induced reductions in the slow PIII component, which is generated by Müller cells responding to light-evoked changes in the extracellular K+ concentration. 6. Lysophosphatidic acid (LPA), a component of serum, had effects on Müller cells that were qualitatively similar to those induced by serum. 7. Our observations demonstrate that exposure to serum alters the activity of multiple types of ion channels in Müller glial cells of the mammalian retina. When there is a breakdown of the blood-retina barrier, LPA may be one of the serum-derived molecules which regulates the physiology of Müller cells.