Nitric oxide/cGMP-induced inhibition of calcium and chloride currents in retinal pericytes

In the CNS, contractile pericytes positioned on endothelium-lined lumens ap pear to play a role in regulating capillary blood flow. This function may b e particularly important in the retina where pericytes are more numerous th an in other tissues. Despite the importance of pericytes, knowledge of the effects of vasoactive molecules, such as nitric oxide (NO), on the physiolo gy of these cells is limited. Since it is likely that ion channels play a r ole in the response of pericytes to signaling molecules from other cells, w e used the perforated-patch configuration of the patch-clamp technique to r ecord the whole-cell currents of pericytes located on microvessels freshly isolated from the rat retina. We found that voltage-gated calcium currents and calcium-activated chloride currents were inhibited during exposure to t he NO donor, sodium nitroprusside (SNP). 8-Bromo-cyclic guanosine monophosp hate (cGMP) mimicked these effects. In contrast, neither SNP nor the cGMP a nalog significantly affected the potassium or nonspecific cation conductanc es, which establish the resting membrane potential of retinal pericytes. Co nsistent with endogenous NO suppressing pericyte channel activity, exposure of isolated microvessels to an inhibitor of NO synthase increased the calc ium and chloride currents. Since our experiments indicate that chloride cha nnel activity is dependent, in part, upon the function of voltage-gated cal cium channels, we postulate that a NO/cGMP-mediated inhibition of calcium c hannels reduces calcium influx and, thereby, lessens the opening of the cal cium-activated chloride channels. This may be one mechanism by which NO dec reases the contractile tone of pericytes. (C) 2001 Academic Press.