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Andrey V Dmitriev, Robert A Linsenmeier; K-ATP channels protect the retina at critical early stages of ischemia. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5896.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of K-ATP channels in stabilization of ionic homeostasis at earlier stages of ischemia.
To characterize the disturbances of ionic homeostasis during ischemia we measured local electrical responses to light (LERG) and both steady state levels and light-induced changes of extracellular concentrations of K+ and Ca++ in the isolated mouse retina using appropriate microelectrodes. An oxygen-glucose deprivation protocol (OGD) was used to mimic ischemia, and glybenclamide (0.1 mM) was applied to block K-ATP channels.
30 minutes of OGD reversibly suppressed the light-induced activity of the retina. The bipolar cell-dependent b-wave of the ERG started to decline already 1 minute after the onset of OGD and completely disappeared in 4-5 minutes. The photoreceptor-dependent slow PIII component of the ERG was less sensitive, but also was suppressed after 15 – 20 minutes. Similarly, the light-induced increase of [K+]o in the inner retina disappeared in 5 minutes, while the decrease of [K+]o in the photoreceptor layer diminished, but still persisted for at least 20 minutes. Right after OGD ended all these responses began to recover, and after 30 minutes their amplitudes were close to the pre-ischemic values, with the exception of the b-wave, which only partly recovered. OGD also evoked reversible changes in ionic concentration: an increase of [K+]o and a decrease of [Ca++]o. These concentration changes were expected, but their rather modest amplitudes (up to 10 – 12 mM for [K+]o and 0.8 mM for [Ca++]o) were surprising. The changes were much more dramatic when the K-ATP channel blocker glybenclamide was applied during OGD. In the inner retina [K+]o increased more than 10 times (up to 40 mM) and [Ca++]o decreased about 4 times (down to 0.3 mM). The recovery rate after OGD with glybenclamide was significantly reduced compared to recovery after OGD alone.
1) Ischemia disturbs first the ability of the retina to respond to light. But the retina can recover if ischemia does not reach the point of failure of ionic homeostasis. 2) K-ATP channels play a role in natural protection from ischemia, delaying the collapse of ionic homeostasis. Blocking K-ATP channels disarms the retina and leads to catastrophic ionic disturbances with unrepairable consequences. 3) A promising strategy against ischemia might be the mobilization of K-ATP channel based defense, possibly using preconditioning.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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