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 β-adrenoreceptors stimulation causes RP depolarization and hyperpolarization, respectively, at least in rats. The intracellular mechanisms of α₁- and β-adrenoreceptors-dependent RP drifts are not investigated. Adenylate cyclase (AC) activator forscolin similarly to selective β-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 α₁-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 β-agonists effects in PV. In addition, α-adrenoreceptors-dependent depolarization in rat PV myocardium could be independent on PLC and PKC.

миокардиальная обкладка, легочные вены, потенциал покоя, адренергическая регуляция, протеинкиназа С, ингибиторы протеинкиназы А, аритмия, myocardial sleeves, pulmonary veins, resting potential, adrenergic regulation, proteinkinase C, proteinkinase A, arrhythmia

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