In another set of experiments, the brain tissues (striatum, learn more parietal cortex, frontal cortex and cerebellum) were excised after brain microPET/CT imaging of mouse injected with 2-[F-18]fluoro-CP-118,954, and a high striatal uptake was also detected in ex vivo optical and microPET images (ROI analysis: 1.4 %ID/g) and in gamma-counting data (2.1 %ID/g at 50 min post-injection) of the brain tissues. Taken
together, these results demonstrated that 2-[F-18]fluoro-CP-118,954 specifically binds to AChE in mouse brains. (C) 2011 Elsevier Inc. All rights reserved.”
“Objective: Animal and human myocytes demonstrate significant swelling and reduced contractility during exposure to stress (metabolic inhibition, hyposmotic stress, or hyperkalemic cardioplegia), and these detrimental consequences may be inhibited by the addition of diazoxide (adenosine triphosphate-sensitive potassium channel opener) via an unknown mechanism. Both SUR1 and SUR2A subunits
have been localized to the heart, and mouse sarcolemmal adenosine triphosphate-sensitive potassium channels are composed Selleckchem 4-Hydroxytamoxifen of SUR2A/Kir6.2 subunits in the ventricle and SUR1/Kir6.2 subunits in the atria. This study was performed to localize the mechanism of diazoxide by direct probing of sarcolemmal adenosine triphosphate-sensitive potassium channel current and by genetic deletion click here of channel subunits.
Methods: Sarcolemmal adenosine triphosphate-sensitive potassium channel current was recorded in isolated wild-type ventricular mouse myocytes during exposure to Tyrode’s solution, Tyrode’s+100 mu mol/L diazoxide, hyperkalemic cardioplegia, cardioplegia+diazoxide, cardioplegia+100 mu mol/ L pinacidil, or metabolic inhibition using whole-cell voltage clamp (N = 7-12 cells per group). Ventricular myocyte volume was measured from SUR1(-/-) and wild-type mice during exposure to control solution, hyperkalemic cardioplegia, or cardioplegia+100 mu mol/ L
diazoxide (N = 7-10 cells per group).
Results: Diazoxide did not increase sarcolemmal adenosine triphosphate-sensitive potassium current in wildtype myocytes, although they demonstrated significant swelling during exposure to cardioplegia that was prevented by diazoxide. SUR1(-/-) myocytes also demonstrated significant swelling during exposure to cardioplegia, but this was not altered by diazoxide.
Conclusions: Diazoxide does not open the ventricular sarcolemmal adenosine triphosphate-sensitive potassium channel but provides volume homeostasis via an SUR1-dependent pathway in mouse ventricular myocytes, supporting a mechanism of action distinct from sarcolemmal adenosine triphosphate-sensitive potassium channel activation.