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This Article Full Text Full Text (PDF) All Versions of this Article: 573/2/483    most recent jphysiol.2006.107102v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matsushita, K. Articles by Puro, D. G. Search for Related Content PubMed PubMed Citation Articles by Matsushita, K. Articles by Puro, D. G. Related Collections Cardiovascular

¹ Department of Ophthalmology & Visual Sciences
² Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA

Although inwardly rectifying potassium (K_IR) channels are known to have important functional roles in arteries and arterioles, knowledge of these channels in pericyte-containing microvessels is limited. A working hypothesis is that K_IR channel activity affects the membrane potential and thereby the contractile tone of abluminal pericytes whose contractions and relaxations may regulate capillary perfusion. Because pericyte function is thought to be particularly important in the retina, we used the perforated-patch technique to monitor the ionic currents of pericytes located on microvessels freshly isolated from the rat retina. In addition, because changes in ion channel function may contribute to microvascular dysfunction in the diabetic retina, we also recorded from pericyte-containing microvessels of streptozotocin-injected rats. Using barium to identify K_IR currents, we found that there is a topographical heterogeneity of these currents in the pericyte-containing microvasculature of the normal retina. Specifically, the K_IR current detected at distal locations is strongly rectifying, but the proximal K_IR current is weakly rectifying and has a smaller inward conductance. However, soon after the onset of diabetes, these differences diminish as the rectification and inward conductance of the proximal K_IR current increase. These diabetes-induced changes were reversed by an inhibitor of polyamine synthesis and could be mimicked by spermine, whose concentration is elevated in the diabetic eye. Hence, spermine is a candidate for mediating the effect of diabetes on the function of microvascular K_IR channels. In addition, our findings raise the possibility that functional changes in K_IR channels contribute to blood flow dysregulation in the diabetic retina.

(Received 7 February 2006; accepted after revision 30 March 2006; first published online 31 March 2006)
Corresponding author D. G. Puro: Department of Ophthalmology and Visual Sciences, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA. Email: dgpuro{at}umich.edu

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