Physiology of rat retinal pericytes: modulation of ion channel activity byserum-derived molecules

1. Pericytes, which are contractile cells located on the outer wall of micr ovessels, are thought to be particularly important in the retina where the ratio of these cells to vascular endothelial cells is the highest of any ti ssue. Retinal pericytes are of interest since they may regulate capillary b lood flow and because their selective loss is an early event in diabetic re tinopathy, which is a common sight-threatening disorder associated with dys function of the blood-retinal barrier. 2. Although a breakdown in the vascular endothelial barrier is a frequent p athophysiological event, knowledge of the effects of blood-derived molecule s on pericyte function is limited. Based on the premise that ion channels p lay a vital role in cellular function, we examined the effect of serum on t he ionic currents of retinal pericytes. To do this, we used the perforated patch configuration of the patch-clamp technique to monitor the whole-cell currents of pericytes located on freshly isolated rat retinal microvessels. 3. Exposure to serum reversibly activated inward and outward currents in vi rtually all of the sampled retinal pericytes. Two types of sustained conduc tances were induced by serum. These were a calcium-permeable non-specific c ation (NSC) current and a voltage-dependent potassium current. In addition, exposure to serum increased the activity of chloride channels which caused transient depolarizing currents. 4. Associated with the activation of these conductances, the membrane poten tial showed a sustained decrease of 10 +/- 2 mV from -56 mV to -46 mV and, also, transient depolarizations to near -30 mV. The serum-induced depolariz ations can activate the voltage-gated calcium channels expressed by the ret inal pericytes. 5. Calcium-permeable NSC channels appear to play a critical role in the res ponse of pericytes to serum-derived molecules. Consistent with this, activa tion of the chloride and potassium channels was sensitive to SK&F 98365, wh ich is a blocker of NSC channels. In addition, chloride and potassium chann el activation was dependent on extracellular calcium. 6. The effects of serum on the activity of channels in retinal pericytes we re qualitatively mimicked by insulin-like growth factor-1 (IGF-1), which is a normal constituent of the blood. 7. There are significant differences in the effects of serum on retinal per icytes compared with vascular smooth muscle cells. Serum activated sustaine d conductances in retinal pericytes but not in the vascular smooth muscle c ells. This suggests a fundamental difference in the mechanisms by which ser um-derived molecules affect these two types of cells. 8. We conclude that serum-derived molecules, such as TGF-1, can activate se veral types of ion channels in retinal pericytes. These changes in channel activity are likely to influence pericyte function at sites of a breakdown in the blood-retinal barrier.