Abstract
Diabetic retinopathy is an important cause of visual loss. Functional abnormalities including vasoconstriction precede structural changes. Using the streptozotocin-model of diabetes in rats, we have identified downregulation of the beta1 subunit of the BK channel in arteriole myocytes as a possible molecular mechanism underlying these early changes. BKbeta1 mRNA levels were reduced as early as one month after induction of diabetes, and BK Ca(2+)-sensitivity and caffeine-evoked BK currents were reduced at three months. This effect appears to be selective for the regulatory subunit, as BKalpha subunit expression was not altered at the mRNA level, and voltage-activated BK currents were unaltered. No changes were seen in voltage activated Ca(2+)-current, Ca(2+)-activated Cl(-)current, or A-type voltage activated K(+)-currents. Reduced Ca(2+)-activated BK activity may promote depolarization, Ca(2+)-channel activation and increased contraction under resting conditions or in response to Ca(2+)-mobilizing agonists.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arterioles / metabolism
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Caffeine / pharmacology
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Calcium / metabolism
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Chlorides / metabolism
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Diabetes Mellitus, Experimental / complications*
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Diabetes Mellitus, Experimental / metabolism
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Diabetes Mellitus, Experimental / physiopathology
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Diabetic Retinopathy / etiology
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Diabetic Retinopathy / metabolism*
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Diabetic Retinopathy / physiopathology
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Down-Regulation
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Large-Conductance Calcium-Activated Potassium Channel beta Subunits / drug effects
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Large-Conductance Calcium-Activated Potassium Channel beta Subunits / genetics
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Large-Conductance Calcium-Activated Potassium Channel beta Subunits / metabolism*
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism*
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Muscle, Smooth, Vascular / physiopathology
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Myocytes, Smooth Muscle / drug effects
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Myocytes, Smooth Muscle / metabolism*
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Potassium / metabolism
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Protein Subunits
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RNA, Messenger / metabolism
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Rats
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Retinal Artery / metabolism
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Vasoconstriction
Substances
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Chlorides
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Large-Conductance Calcium-Activated Potassium Channel beta Subunits
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Protein Subunits
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RNA, Messenger
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Caffeine
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Potassium
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Calcium