Diadenosine pentaphosphate (Ap5A) belongs to the family of diadenosine polyphosphates, endogenously produced compounds that affect vascular tone and cardiac performance when released from platelets. The previous findings indicate that Ap5A shortens action potentials (APs) in rat myocardium via activation of purine P2 receptors. The present study demonstrates alternative mechanism of Ap5A electrophysiological effects found in guinea pig myocardium. Ap5A (10 M) shortens APs in guinea pig working atrial myocardium and slows down pacemaker activity in the sinoatrial node. P1 receptors antagonist DPCPX (10 M) or selective GIRK channels blocker tertiapin (10 M) completely abolished all Ap5A effects, while P2 blocker PPADS (10 M) was ineffective. Patch-clamp experiments revealed potassium inward rectifier current activated by Ap5A in guinea pig atrial myocytes. The current was abolished by DPCPX or tertiapin and therefore was considered as potassium acetylcholine-dependent inward rectifier (I ). Thus, unlike rat, in guinea pig atrium Ap5A produces activation of P1 receptors and subsequent opening of KACh channels leading to negative effects on cardiac electrical activity.

We studied the effect of extracellular purine nucleotides (NAD and ATP) on spontaneous arrhythmogenic activity caused by norepinephrine in myocardial sleeves of pulmonary veins. In pulmonary veins, NAD and ATP reduced the frequency of action potentials and their duration at regular type of spontaneous activity caused by norepinephrine. NAD and ATP lengthened the intervals between spike bursts at periodic (burst) type of spontaneous activity. In addition, ATP shortened the duration of spike bursts and the number of action potentials in the "bursts" caused by norepinephrine in the pulmonary veins. It was hypothesized that NAD and ATP attenuate the effects of sympathetic stimulation and when released together with norepinephrine from sympathetic endings in vivo, probably, reduce arrhythmogenic activity in myocardial sleeves of pulmonary veins.

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We have demonstrated the phenomenon of Са(2+)-induced hyperpolarization in the myocardium of pulmonary veins (PVs) in rats. An increase in cytoplasmic calcium [Са(2+)] i was shown to shift the resting potential (RP) in the PVs towards more negative values. The compounds inducing an increase in [Са(2+)] i , such as isoproterenol (10 μM), caffeine (5 mM), and ryanodine (0.01 μM), caused hyperpolarization of 10 ± 2, 9 ± 1.3, and 4.1 ± 2 mV, respectively. The inhibition of calcium-dependent potassium currents (IKCa) did not change RP of PVs under the control conditions and did not affect the Са(2+)-induced hyperpolarization.