Key result
Beta-adrenergic stimulation with isoproterenol induced a 10±2 mV hyperpolarization partially mediated by PKA, whereas alpha1-adrenergic stimulation with phenylephrine caused a 20±2 mV depolarization independent of PLC and PKC.
Why the study?
Does adrenergic stimulation alter resting membrane potential in rat pulmonary vein myocardium via specific intracellular signaling pathways?
Does adrenergic stimulation alter resting membrane potential in rat pulmonary vein myocardium via specific intracellular signaling pathways?
Mean Difference: 10
p-value: p=<0.05
Beta-adrenergic hyperpolarization in rat pulmonary vein myocardium is partially mediated by the cAMP/PKA pathway, while alpha-adrenergic depolarization appears independent of PLC and PKC.
Suggests adrenergic modulation of pulmonary vein electrophysiology; hypothesis-generating and requires validation in human models.
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 α-adrenoreceptors-dependent phenylephrine-induced depolarization in rat PV myocardium. These results allow us to suggest that β-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.
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Каримова et al. (2017) studied Pulmonary vein myocardium electrophysiology (n=78). Isoproterenol and Phenylephrine vs. Baseline resting potential was evaluated on Change in resting membrane potential (hyperpolarization with isoproterenol) (10±2 mV, p=<0.05). Beta-adrenergic stimulation with isoproterenol induced a 10±2 mV hyperpolarization partially mediated by PKA, whereas alpha1-adrenergic stimulation with phenylephrine caused a 20±2 mV depolarization independent of PLC and PKC.
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