Topographical heterogeneity of K(IR) currents in pericyte-containing microvessels of the rat retina: effect of diabetes.

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.