Okay. Correct answer is B, adenosine activation of A1 receptors. What are the observations here? Well, the observations are a decrease or more negative voltage in the maximal diastolic potential pointed out here by the arrows. Slowing of phase IV diastolic depolarization, that is flattening of this slope in the solid versus the dotted line, and a subtle shortening of the action potential duration. Now, if Aberdeen will slow phase IV diastolic depolarization by blocking IF, but will not make the maximal diastolic potential more negative. Late sodium current block by ranolazine is not likely to have a large impact here. Now, amiodarone could slow phase IV, but not likely by IKS block and might prolong the action potential a bit more. Adenosine, by its both direct and indirect effects, will make the maximum diastolic potential MDP more negative, will slow phase IV, and will shorten the action potential, hence is the best answer. Now, if we consider the mechanism of action of this nucleoside produced in the cell that is transported across the cell membrane, and is metabolized both extracellularly and intracellularly by a number of different mechanisms, adenosine has several effects. It's got a direct effect on adenosine receptors. These are G-protein coupled receptors, and it activates this receptor, and it activates not only the adenosine receptor, but IKACH receptor. This leads to the opening of a potassium channel. This potassium channel hyperpolarizes because positive charge flows out of the cell because of the concentration gradient of potassium in both atrial and nodal tissue, and it shortens the action potential duration because of this outwardly directed current. There are also indirect effects of adenosine by inhibition of adenylyl cyclase. Adenosine itself is anti-adrenergic, also inhibits calcium current, and in doing so will shorten the atrial action potential duration. The multiple effects of adenosine are responsible for the effects on those nodal action potentials shown previously. A couple of things to consider. Adenosine has its effect and impact by working on these adenosine receptors from the extracellular side of the membrane, but it's transported across the membrane, and this is one of the ways in which it's inactivated. Dipyridamols will block this transport, so may potentiate the effect of adenosine, and you need to make sure that you take that into consideration when administering adenosine to a patient. In order to block the effect of adenosine, methylxanthines are blockers of the adenosine receptor and can abrogate the effect of adenosine on the cardiac rhythm.

Adenosine

Cardiac electrophysiology

G-protein coupled receptors

IKACH

Hyperpolarization