PDF Effects of Extracellular Adenosine and ATP on Cardiomyocytes

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If there are large amounts of ATP hydrolyzed, and especially if there is insufficient oxygen available i.

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Adenosine can bind to purinergic receptors in different cell types where it can produce a number of different physiological actions. One important action is vascular smooth muscle relaxation, which leads to vasodilation. This is a particularly important mechanism for matching coronary blood flow to the metabolic needs of the heart. In coronary vascular smooth muscle, adenosine binds to adenosine type 2A A 2A receptors, which are coupled to the Gs-protein. Activation of this G-protein stimulates adenylyl cyclase AC in figure , increases cAMP and causes protein kinase activation.

This stimulates K ATP channels, which hyperpolarizes the smooth muscle, causing relaxation. Increased cAMP also causes smooth muscle relaxation by inhibiting myosin light chain kinase , which leads to decreased myosin phosphorylation and a decrease in contractile force. There is also evidence that adenosine inhibits calcium entry into the cell through L-type calcium channels.

Since calcium regulates smooth muscle contraction , reduced intracellular calcium causes relaxation. In some types of blood vessels, there is evidence that adenosine produces vasodilation through increases in cGMP , which leads to inhibition of calcium entry into the cells as well as opening of potassium channels. In cardiac tissue, adenosine binds to type 1 A 1 receptors, which are coupled to Gi-proteins. Activation of this pathway opens potassium channels, which hyperpolarizes the cell.

Activation of the Gi-protein also decreases cAMP, which inhibits L-type calcium channels and therefore calcium entry into the cell.

In cardiac pacemaker cells located in the sinoatrial node, adenosine acting through A 1 receptors inhibits the pacemaker current I f , which decreases the slope of phase 4 of the pacemaker action potential thereby decreasing its spontaneous firing rate negative chronotropy. Inhibition of L-type calcium channels also decreases conduction velocity negative dromotropic effect particularly at the atrioventricular AV nodes.

Finally, adenosine by acting on presynaptic purinergic receptors located on sympathetic nerve terminals inhibits the release of norepinephrine. In terms of its electrical effects in the heart, adenosine decreases heart rate and reduces conduction velocity, especially at the AV node, which can produce atrioventricular block.

Purinergic Inhibition of Glucose Transport in Cardiomyocytes

Note, however, that when adenosine is infused into humans, heart rate increases because of baroreceptor reflexes caused by systemic vasodilation and hypotension. Adenosine has a very short half-life.


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In human blood, its half-life is less than 10 seconds. There are two important metabolic fates for adenosine.

Effects Of Extracellular Adenosine And Atp On Cardiomyocytes 1998

Objective: Potassium channel openers target ATP sensitive potassium K ATP channels, and might be beneficial in the treatment of ischaemic cardiac conditions. Ischaemia is associated with an increase in the concentrations of intracellular nucleoside diphosphates and protons, two regulators of K ATP channels. Since it is largely unknown whether these factors modulate the action of potassium channel openers, the aim of this study was to define the effects of ADP and intracellular acidification on K ATP channel activation by nicorandil, a potassium channel opener currently in clinical use.

Cardiac Action Potential, Animation.

Methods: To measure ionic currents, the whole cell patch clamp technique was employed in guinea pig single ventricular myocytes. Induction of K ATP channel current by pinacidil, a potassium channel opener chemically unrelated to nicorandil, was used for comparison.

Therapeutic and Diagnostic Use and Rationale

ADP in the pipette solution was required for the nicorandil induced activation of K ATP channels when the pH of the pipette solution was 7. In the absence of ADP, lowering the pH of the pipette solution to 6. Conclusions: Nicorandil may activate K ATP channel current more effectively in conditions associated with a change in intracellular proton and ADP concentrations such as cardiac ischaemia. Intracellular acidification and ADP enhance nicorandil induction of ATP sensitive potassium channel current in cardiomyocytes.

Ischaemia is associated with an increase in the concentrations of intracellular nucleoside diphosphates and protons, two regulators of KATP channels. Since it is largely unknown whether these factors modulate the action of potassium channel openers, the aim of this study was to define the effects of ADP and intracellular acidification on KATP channel activation by nicorandil, a potassium channel opener currently in clinical use.

Induction of KATP channel current by pinacidil, a potassium channel opener chemically unrelated to nicorandil, was used for comparison. ADP in the pipette solution was required for the nicorandil induced activation of KATP channels when the pH of the pipette solution was 7. Conclusions: Nicorandil may activate KATP channel current more effectively in conditions associated with a change in intracellular proton and ADP concentrations such as cardiac ischaemia.

Cardiovascular Medicine.