Nitric oxide/cGMP-induced inhibition of calcium and chloride currents in retinal pericytes.
In the CNS, contractile pericytes positioned on endothelium-lined lumens appear to play a role in regulating capillary blood flow. This function may be particularly important in the retina where pericytes are more numerous than in other tissues. Despite the importance of pericytes, knowledge of the effects of vasoactive molecules, such as nitric oxide (NO), on the physiology of these cells is limited. Since it is likely that ion channels play a role in the response of pericytes to signaling molecules from other cells, we used the perforated-patch configuration of the patch-clamp technique to record 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 the NO donor, sodium nitroprusside (SNP). 8-Bromo-cyclic guanosine monophosphate (cGMP) mimicked these effects. In contrast, neither SNP nor the cGMP analog significantly affected the potassium or nonspecific cation conductances, which establish the resting membrane potential of retinal pericytes. Consistent with endogenous NO suppressing pericyte channel activity, exposure of isolated microvessels to an inhibitor of NO synthase increased the calcium and chloride currents. Since our experiments indicate that chloride channel activity is dependent, in part, upon the function of voltage-gated calcium channels, we postulate that a NO/cGMP-mediated inhibition of calcium channels reduces calcium influx and, thereby, lessens the opening of the calcium-activated chloride channels. This may be one mechanism by which NO decreases the contractile tone of pericytes.
Sakagami
K
K
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA.
Kawamura
H
H
Wu
D M
DM
Puro
D G
DG
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D008751:Methylene Blue / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012171:Retinal Vessels / Q000166:cytology; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology
D002712:Chlorides; D004791:Enzyme Inhibitors; D007473:Ion Channels; D014665:Vasodilator Agents; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D006152:Cyclic GMP; D009543:Nifedipine; D002118:Calcium; D008751:Methylene Blue