PDGF-induced coupling of function with metabolism in microvascular pericytes of the retina.
OBJECTIVE
The aim of this study was to test the hypothesis that platelet-derived growth factor (PDGF)-BB regulates the physiology of retinal pericytes, which are contractile cells located on the abluminal surface of capillaries. The expression of PDGF-BB and its cognate receptor in retinal vessels suggests a vasoactive function. However, although endothelium-derived PDGF-BB appears vital for the development of pericyte-containing microvessels, its role in the mature vasculature remains uncertain.


METHODS
Based on the premise that ion channels mediate the responses of pericytes to vasoactive signals, the perforated-patch configuration of the patch-clamp technique was used to determine the effect of PDGF-BB on the ionic currents and membrane potential of pericytes located on microvessels freshly isolated from the adult rat retina. Changes in pericyte calcium levels were monitored with the calcium indicator fluo-4. Differential interference contrast optics and image analysis software aided in assessing the effects of PDGF-BB on the lumens of isolated pericyte-containing microvessels. In some experiments, blockers of adenosine triphosphate (ATP) synthesis created chemical ischemia.


RESULTS
Electrophysiological recordings from pericytes showed that PDGF-BB can activate nonspecific cation channels, chloride channels, and ATP-sensitive potassium channels. The metabolic status of an isolated capillary determined which of these ion channels were activated by PDGF-BB and thereby whether the membrane potential decreased or increased, the cell calcium rose or fell, and the vessel lumen constricted or dilated.


CONCLUSIONS
The ability of PDGF-BB to be a vasoconstrictor when energy supplies are ample and to be a vasodilator under ischemic conditions may provide an efficient mechanism to link capillary function to local metabolic needs.
Sakagami
K
K
Department of Ophthalmology and Visual Sciences, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA.
Kodama
T
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Puro
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D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D000077214:Becaplermin; D002118:Calcium / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D017136:Ion Transport; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D020286:Pericytes / Q000187:drug effects / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism*; D014966:Xanthenes / Q000378:metabolism
D000814:Aniline Compounds; C409648:Fluo 4; D007473:Ion Channels; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D014966:Xanthenes; D000077214:Becaplermin; D002118:Calcium