Attenuation of inward rectifier potassium current contributes to the α1‐adrenergic receptor‐induced proarrhythmicity in the caval vein myocardium

Abstract

Aim This study is aimed at investigation of electrophysiological effects of α1‐adrenoreceptor (α1‐AR) stimulation in the rat superior vena cava (SVC) myocardium, which is one of the sources of proarrhythmic activity. Methods α1‐ARs agonists (phenylephrine—PHE or norepinephrine in presence of atenolol—NE + ATL) were applied to SVC and atrial tissue preparations or isolated cardiomyocytes, which were examined using optical mapping, glass microelectrodes or whole‐cell patch clamp. α1‐ARs distribution was evaluated using immunofluorescence. Kir2.X mRNA and protein level were estimated using RT‐PCR and Western blotting. Results PHE or NE + ATL application caused a significant suppression of the conduction velocity (CV) of excitation and inexcitability in SVC, an increase in the duration of electrically evoked action potentials (APs), a decrease in the maximum upstroke velocity (dV/dtmax) and depolarization of the resting membrane potential (RMP) in SVC to a greater extent than in atria. The effects induced by α1‐ARs activation in SVC were attenuated by protein kinase C inhibition (PKC). The whole‐cell patch clamp revealed PHE‐induced suppression of outward component of IK1 inward rectifier current in isolated SVC, but not atrial myocytes. These effects can be mediated by α1A subtype of α‐ARs found in abundance in rat SVC. The basal IK1 level in SVC was much lower than in atria as a result of the weaker expression of Kir2.2 channels. Conclusion Therefore, the reduced density of IK1 in rat SVC cardiomyocytes and sensitivity of this current to α1A‐AR stimulation via PKC‐dependent pathways might lead to proarrhythmic conduction in SVC myocardium by inducing RMP depolarization, AP prolongation, CV and dV/dtmax decrease.

Automatic Activity Arising in Cardiac Muscle Sleeves of the Pulmonary Vein

“…Although this review focuses on the physiology of the PV myocardial sleeves, similar results have also been observed in the rat superior vena cava (SVC) and azygos vein [ 31 , 45 , 72 ], in which myocardial sleeves also extend and constitute a source of arrhythmia in humans [ 2 ]. The effects of age on the induction of CAA in the SVC and PV was also explored [ 31 ].…”

“…The mechanism under-laying depolarization resulting from α-adrenergic stimulation remains to be determined. In a different preparation of the rat superior vena cava, depolarization by phenylephrine was associated with reduction of the background Kir 2.1 current [ 45 ].…”

Electroacupuncture Ameliorates Acute Myocardial Ischemic Injury and Long QT Interval in Mice through the α1A-Adrenergic Receptor: Electrophysiological, Morphological, and Molecular Evidence

“…Furthermore, the effect of catecholamine on isolated mouse heart ischemia-induced arrhythmias is mediated mainly by WB 4101-sensitive α 1A -AR activation [ 35 ]. Since catecholamines induce α 1 -AR activation during MI, the increased expression of α 1A -AR is closely related to arrhythmia after MI [ 18 , 20 , 36 , 37 ]. MI-induced acquired LQTS, characterized by significant changes in QT interval length on ECG, is a prime cause of VA and sudden cardiac death in patients.…”

Getting it right matters! Covid‐19 pandemic analogies to everyday life in medical sciences

“…Great. After all a lot of scientists are all too familiar with PCRs, so there is not much to learn there 12‐16 . We made some assumptions and visualized a statistical concept which most of us would admit we had not been fully considering before the pandemic.…”

“…After all a lot of scientists are all too familiar with PCRs, so there is not much to learn there. 12 , 13 , 14 , 15 , 16 We made some assumptions and visualized a statistical concept which most of us would admit we had not been fully considering before the pandemic. So, this is it, we can all go (or stay) home and feel satisfied, because we had a little academic workout and a better understanding of screening tests usually only cared about by a narrow circle of physicians?…”