Physiology of XXXX retinal pericytes: modulation of ion channel activity by serum-derived molecules.

@entity972 @entity6 @entity2865 @entity2135 @entity5995 @entity460 @entity35
1. Pericytes, which are contractile cells located on the outer wall of microvessels, are thought to be particularly important in the retina where the ratio of these cells to vascular endothelial cells is the highest of any tissue. Retinal pericytes are of interest since they may regulate capillary blood flow and because their selective loss is an early event in @entity6 , which is a common sight-threatening disorder associated with dysfunction of the blood- @entity5995 barrier. 2. Although a breakdown in the vascular endothelial barrier is a frequent pathophysiological event, knowledge of the effects of blood-derived molecules on pericyte function is limited. Based on the premise that ion channels play a vital role in cellular function, we examined the effect of serum on the 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 @entity35 retinal microvessels. 3. Exposure to serum reversibly activated inward and outward currents in virtually all of the sampled retinal pericytes. Two types of sustained conductances were induced by serum. These were a @entity460 -permeable non-specific cation (NSC) current and a voltage-dependent @entity972 current. In addition, exposure to serum increased the activity of @entity2865 channels which caused transient depolarizing currents. 4. Associated with the activation of these conductances, the membrane potential 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 depolarizations can activate the voltage-gated @entity460 channels expressed by the retinal pericytes. 5. @entity460 -permeable NSC channels appear to play a critical role in the response of pericytes to serum-derived molecules. Consistent with this, activation of the @entity2865 and @entity972 channels was sensitive to SK_F 96365, which is a blocker of NSC channels. In addition, @entity2865 and @entity972 channel activation was dependent on extracellular @entity460 . 6. The effects of serum on the activity of channels in retinal pericytes were qualitatively mimicked by @entity2135 ( @entity2135 ), which is a normal constituent of the blood. 7. There are significant differences in the effects of serum on retinal pericytes compared with vascular smooth muscle cells. Serum activated sustained conductances in retinal pericytes but not in the vascular smooth muscle cells. This suggests a fundamental difference in the mechanisms by which serum-derived molecules affect these two types of cells. 8. We conclude that serum-derived molecules, such as @entity2135 , can activate several 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.
