Selective downregulation of the BKβ1 subunit in diabetic arteriolar myocytes
MK McGahon, X Zhang, CN Scholfield, TM Curtis… - Channels, 2007 - Taylor & Francis
MK McGahon, X Zhang, CN Scholfield, TM Curtis, JG McGeown
Channels, 2007•Taylor & FrancisDiabetic 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 down-regulation of the β1 subunit of the BK channel in arteriole
myocytes as a possible molecular mechanism underlying these early changes. BKβ1 mRNA
levels were reduced as early as 1 month after induction of diabetes, and BK Ca2+-sensitivity
and caffeine-evoked BK currents were reduced at 3 months. This effect appears to be …
vasoconstriction precede structural changes. Using the streptozotocin-model of diabetes in
rats, we have identified down-regulation of the β1 subunit of the BK channel in arteriole
myocytes as a possible molecular mechanism underlying these early changes. BKβ1 mRNA
levels were reduced as early as 1 month after induction of diabetes, and BK Ca2+-sensitivity
and caffeine-evoked BK currents were reduced at 3 months. This effect appears to be …
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 down-regulation of the β1 subunit of the BK channel in arteriole myocytes as a possible molecular mechanism underlying these early changes. BKβ1 mRNA levels were reduced as early as 1 month after induction of diabetes, and BK Ca2+-sensitivity and caffeine-evoked BK currents were reduced at 3 months. This effect appears to be selective for the regulatory subunit, as BKα subunit expression was not altered at the mRNA level, and voltage-activated BK currents were unaltered. No changes were seen in voltage activated Ca2+-current, Ca2+-activated Cl--current, or A-type voltage activated K+-currents. Reduced Ca2+-activated BK activity may promote depolarization, Ca2+-channel activation and increased contraction under resting conditions or in response to Ca2+-mobilizing agonists.
Taylor & Francis Online