Abstract
Purpose: :
Knowledge of the functional organization of the retinal microvasculature is limited despite its physiological and pathobiologial importance. Here, we tested the hypothesis that functional KATP channels are heterogeneously distributed within retinal arteriole/capillary complexes. KATP channels are of interest because they mediate the effects of vasoactive signals, such as adenosine.
Methods: :
Voltages and currents were monitored via perforated-patch pipettes attached to mural cells located on microvascular complexes freshly isolated from the adult rat retina, as detailed previously. Using pinacidil-filled micropipettes, this KATP activator was focally applied onto isolated microvessels. In some experiments, we used a micromanipulator-controlled pipette to cut isolated microvessels into proximal and distal segments.
Results: :
In a series of 20 experiments, pinacidil was systematically applied at sites throughout branching microvascular complexes. At proximal locations within ~450 µm of a smooth muscle-encircled arteriole, KATP channel activation was minimal. In contrast, markedly greater (p < 0.001) voltage changes were detected at more distal sites, i.e. within the capillaries. In other experiments, the KATP conductance activated by pinacidil (n = 9) or adenosine (n = 6) was quantified before and after cutting a microvessel into its proximal and distal portions. Consistent with a heterogeneous distribution of functional KATP channels, currents were induced almost exclusively (p ≤ 0.001) in the distal, as compared to the proximal, portion of the microvascular tree.
Conclusions: :
In the microvasculature of the rat retina, functional KATP channels are chiefly located in the capillaries. Based on this topographical distribution and our recent characterization of the electronic architecture of retinal microvessels, we postulate that an adenosine-induced vasodilation of a smooth-muscle encircled arteriole is dependent upon the activation of capillary KATP channels whose hyperpolarizing effect is electrotonically transmitted via gap junction pathways to proximal KATP-deficient sites.
Keywords: retina • blood supply • ion channels