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D.M. Wu, D.G. Puro; Topographical Distribution of KATP Channels in the Retinal Microvaculature . Invest. Ophthalmol. Vis. Sci. 2003;44(13):354.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The pericyte-containing microvasculature of the retina is likely to play a key role in regulating local perfusion. However, knowledge of the functional organization of retinal capillaries is limited, although it is known that gap junction pathways result in extensive intercellular communication within these vessels. We propose that there are regions of functional specialization in retinal capillaries. To test this hypothesis, we mapped the distribution of functional KATP channels, which are activated by vasoactive signals such as dopamine and adenosine. Methods: Papain-treated rat retinas were gently pressed between two glass coverslips. Complexes of retinal microvessels adhered to the glass. Dual patch-clamp recordings enabled simultaneous monitoring of current or voltage from pairs of recording sites located hundreds of microns apart within a capillary plexus. To map the topographical distribution of KATP channels, a puffer pipet containing the selective KATP channel opener pinacidil was systematically moved along capillary branches . Results: In 9 freshly isolated pericyte-containing microvessels in which we successfully obtained patch-clamp recordings from two sites and also surveyed the topography of pinacidil sensitivity, electrotonic transmission between recording sites was observed in each case. Further evidence for intercellular communication was a synchronicity in the spontaneous current fluctuations seen at the two recording sites. In 6 of the 9 microvessels, we observed a topographical distribution in the ability of locally applied pinacidil to activate a hyperpolarizing current. In 5 of these 6 microvessels, one recording site was in a pinacidil-sensitive region of the capillary network, while the other was in a region where focal application of pinacidil resulted in no detectable current. Pinacidil application in the sensitive region resulted in a hyperpolarization at both recording sites due to electrotonic transmission. Conversely, voltage at neither site was affected when pinacidil was applied in the unresponsive region of the capillary plexus. In the 6th microvessel, regions were found that varied in their degree of response to pinacidil; focal pinacidil application induced twice as much hyperpolarization in some regions as compared with others. Conclusions: Within the retinal microvasculature, there is a topographical distribution of sensitivity to the KATP channel opener pinacidil. Spatial variations in the density of ion channels is a previously unrecognized microvascular specialization that may play a vital role in regulating capillary perfusion to meet local metabolic needs.
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