α1-adrenergic receptors accompanied by GATA4 expression are related to proarrhythmic conduction and automaticity in rat interatrial septum

J Physiol Biochem. 2022 Nov;78(4):793-805. doi: 10.1007/s13105-022-00902-8. Epub 2022 Jul 8.

Abstract

The development of interatrial septum (IAS) is a complicated process, which continues during postnatal life. The hypertrophic signals in developing heart are mediated among others by α-adrenergic pathways. These facts suggest the presence of specific electrophysiological features in developing IAS. This study was aimed to investigate the electrical activity in the tissue preparations of IAS from rat heart in normal conditions and under stimulation of adrenoreceptors. Intracellular recording of electrical activity revealed less negative level of resting membrane potential in IAS if compared to myocardium of left atrium. In normal conditions, non-paced IAS preparations were quiescent, but noradrenaline (10-5 M) and phenylephrine (10-5 M) induced spontaneous action potentials, which could be abolished by α1-blocker prazosin (10-5 M), but not β1-blocker atenolol (10-5 M). Optical mapping showed drastic phenylephrine-induced slowing of conduction in adult rat IAS. The α1-dependent ectopic automaticity of IAS myocardium might be explained by immunohistochemical data indicating the presence of transcription factor GATA4 and abundant α1A-adrenoreceptors in myocytes from adult rat IAS. An elevated sensitivity to adrenergic stimulation due to involvement of α1-adrenergic pathways may underlie increased proarrhythmic potential of adult IAS at least in rats.

Keywords: Action potential; Adrenoreceptors; Arrhythmia; Heart; Interatrial septum; Oval fossa.

MeSH terms

  • Adrenergic Agents
  • Animals
  • GATA4 Transcription Factor / genetics
  • Heart Atria / metabolism
  • Phenylephrine / pharmacology
  • Prazosin* / pharmacology
  • Rats
  • Receptors, Adrenergic, alpha-1* / metabolism

Substances

  • Receptors, Adrenergic, alpha-1
  • Prazosin
  • Phenylephrine
  • Adrenergic Agents
  • Gata4 protein, rat
  • GATA4 Transcription Factor