Abstract
Purpose: :
Although retinal perfusion is altered early in the course of diabetes, the mechanisms for this remain uncertain. In the study, we tested the hypothesis that diabetes affects the function of inwardly rectifying potassium (KIR) channels in the pericyte–containing retinal microvasculature. These channels are of interest because they are likely to play a role in regulating the responsiveness of microvessels to vasoactive signals.
Methods: :
Freshly isolated complexes of microvessels were obtained from papain–treated rat retinas. Diabetes was induced by streptozotocin. Ionic currents were monitored in abluminal pericytes via perforated–patch pipettes.
Results: :
In recordings from pericytes located in the distal portions of retinal microvessels (n = 28), we detected a barium–sensitive current that showed strong inward rectification. Consistent with this being a KIR current, the reversal potential of this current closely matched the equilibrium potential for K+. In addition, increasing extracellular potassium increased the conductance of this current. In contrast to the steeply rectifying KIR current detected at distal sites, the KIR current at proximal sites within the retinal microvasculature had a significantly (P < 0.001) lower conductance and was only weakly rectifying (n = 40). Interestingly, after 3 weeks of experimental diabetes, the proximal KIR current became strongly rectifying (n = 10). Because polyamines are increased in the retinas of diabetics and are known to regulate KIR channel function, we assessed the effect of spermine freshly isolated non–diabetic on microvessels (n = 6). Within 15 min, this polyamine (5 mM) caused the proximal KIR current to become strongly rectifying; this was a reversible effect.
Conclusions: :
Our experiments indicate that there are functional differences in the KIR channels located at proximal and distal sites within the pericyte–containing retinal microvasculature. Our results also show that diabetes alters the physiology of the proximal KIR channels. We propose that polyamines may play a role in mediating the effect of diabetes on these channels. A diabetes–induced increase in KIR rectification would enhance the depolarizing effect of vasoactive signals and thereby, alter microvascular function.
Keywords: diabetic retinopathy • vascular cells • ion channels