Mitochondrial potassium ATP channels and retinal ischemic preconditioning.

Investigative Ophthalmology & Visual Science
Steven RothVytautus Bindokas

Abstract

To examine the mechanisms of ischemic preconditioning (IPC) related to the opening of mitochondrial KATP (mKATP) channels in the retina. Rats were subjected to retinal ischemia after IPC, or retinas were rendered ischemic after pharmacological opening of mKATP channels. The effects of blocking mKATP channel opening, nitric oxide synthase (NOS) subtypes, or protein kinase C (PKC) on the protective effect of IPC or on the opening of mKATP channels were studied. Electroretinography assessed functional recovery after ischemia. Immunohistochemistry and image analysis were used to measure changes in levels of reactive oxygen species (ROS) and NOS subtypes and to determine their cellular localization. IPC was effectively mimicked by injection of the mKATP channel opener diazoxide. Both IPC and its mimicking by diazoxide were completely attenuated by the mKATP channel blocker 5-hydroxydecanoic acid (5-HD). Nonspecific blockade of NOS by N(omega)-nitro-L-arginine (L-NNA), but not by specific inducible (i)NOS or neuronal (n)NOS inhibitors, blunted IPC and IPC-mimicking, as did blockade of PKC. IPC and diazoxide IPC-mimicking significantly enhanced mitochondrial ROS production in the inner retina, an effect blocked by 5-HD. Mitochondrial ...Continue Reading

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Citations

May 17, 2011·Journal of Molecular Neuroscience : MN·John C DreixlerSteven Roth
Mar 22, 2008·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Shahid Husain, David E Potter
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Jun 20, 2013·Investigative Ophthalmology & Visual Science·Uttio Roy ChowdhuryMichael P Fautsch
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Nov 26, 2010·Experimental Eye Research·John C DreixlerSteven Roth
Jul 28, 2009·Experimental Eye Research·John C DreixlerSteven Roth
Aug 30, 2008·Experimental Eye Research·John C DreixlerSteven Roth
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Mar 27, 2009·Anesthesiology·John C DreixlerSteven Roth
Mar 9, 2021·Clinical and Experimental Pharmacology & Physiology·Tajamul H MirAariba Zahoor

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