[Intracellular Molecular Mechanisms of Adrenergic Regulation of Pulmonary Vein Myocardium Membrane Potential].

Pulmonary vein (PV) myocardium is characterized by numerous electrophysiological properties which make this tissue highly prone to spontaneous, ectopic activity partially due to resting potential (RP) instability. PV derived ectopy frequently underlies supraventricular arrhythmias, including atrial fibrillation. It has also been demonstrated that adrenergic stimulation causes proarrhythmic alterations in PV. Selective α1- and ß-adrenoreceptors stimulation causes RP depolarization and hyperpolarization, respectively, at least in rats. The intracellular mechanisms of α1- and ß-adrenoreceptors-dependent RP drifts are not investigated. Adenylate cyclase (AC) activator forscolin similarly to selective ß-adrenoreceptors agonist isoproterenol (ISO) induced strong hyperpolarization in quiescent isolated perfused multicellular preparations of rat PV. Maximal value of hyperpolarization in PV was equal after application of both compounds. Proteinkinase A (PKA) inhibitors КТ5720, H-89 and Rp-adenosine-cAMP suppressed ISO-induced hyperpolarization in PV. Inhibitors of phospholipase C (U73122) or D (FIPI), similarly to proteinkinase C (PKC) inhibitor chelerythrine, failed to suppress α-adrenoreceptors-dependent phenylephrine-induced depolarization in rat PV myocardium. These results allow us to suggest that ß-adrenoreceptors-dependent RP hyperpolarization in quiescent rat PV myocardium is only partially mediated by cAMP-dependent signal transduction pathway and by PKA. Besides, PKA-independent mechanisms also contribute to ß-agonists effects in PV. In addition, α-adrenoreceptors-dependent depolarization in rat PV myocardium could be independent on PLC and PKC.

Effect of Purine Co-Transmitters on Automatic Activity Caused by Norepinephrine in Myocardial Sleeves of Pulmonary Veins.

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.

The role of cytoplasmic calcium in the regulation of the resting potential in the pulmonary veins myocardium in rats and mice.

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.