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ATP-sensitive potassium channels and cardiac protection (part 7)

ATP-sensitive potassium channels and cardiac protection (part 7)

The most potent and highly specific KATP inhibitors are the well known oral antidiabetics derived from sulphonylurea and benzoic acid, such as glibenclamide. This drug blocks KATP channels of pancreatic beta-cells in nanomolar concentrations , whereas cardiac cells are blocked only by micromolar concentrations of glibenclamide . The likely mechanism of action is a change in the affinity of the channel to ATP molecule. The effect of Katp channel inhibitors is potentiated by bivalent cations or by reduction of intracellular pH and is counteracted by Mg-ADP, active G protein and phosphorylation of the channel.
The effects of glibenclamide on ischemic heart are in agreement with the concept of Katp blockade . Yao et al demonstrated that already low doses of glibencla-mide prevented shortening of monophasic action potential during ischemia and impaired recovery from postischemic dysfunction in a dog. An exciting hypothesis was recently proposed by Yokoshiki et al , who reported that inhibition of KATP channels by glibenclamide or tolbutamide (as well as by ATP) may be counteracted by enzymatic destruction of the cytoskeleton’s actin. This finding suggests a kind of mechanical shutting off of the Katp channel. You can now always visit a reliable pharmacy that will take the very best care of you and offer very cheap drugs that work: buy flovent inhaler for you to benefit the most from the treatment and always be at your best.

Category: Cardiology

Tags: ATP-sensitive potassium channel, Ischemic preconditioning, Potassium channel inhibitors, Potassium channel openers

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