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

Acta Physiol (Oxf). 2021 Apr;231(4):e13597. doi: 10.1111/apha.13597. Epub 2020 Dec 20.

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.

Keywords: IK1; arrhythmia; caval veins; inward rectifier current; myocardial sleeves; α-adrenergic receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Heart Atria
  • Myocardium
  • Potassium*
  • Rats
  • Receptors, Adrenergic, alpha-1*
  • Vena Cava, Superior*

Substances

  • Receptors, Adrenergic, alpha-1
  • Potassium

Associated data

  • RefSeq/RRID: AB_2338006