Selective downregulation of the BKbeta1 subunit in diabetic arteriolar myocytes.
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.
McGahon
Mary K
MK
Center for Vision Sciences, School of Biomedical Sciences, The Queen's University of Belfast, Institute of Clinical Sciences, The Royal Victoria Hospital, Belfast, UK.
Zhang
Xiaohong
X
Scholfield
C Norman
CN
Curtis
Timothy M
TM
McGeown
J Graham
JG
D000818:Animals; D001160:Arterioles / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D021122:Protein Subunits; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012161:Retinal Artery / Q000378:metabolism; D014661:Vasoconstriction
D002712:Chlorides; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D021122:Protein Subunits; D012333:RNA, Messenger; D002110:Caffeine; D011188:Potassium; D002118:Calcium