Modulation of cardiac ionic homeostasis by 3-iodothyronamine

Sandra Ghelardoni, Silvia Suffredini, Sabina Frascarelli, Simona Brogioni, Grazia Chiellini, Simonetta Ronca-Testoni, David K. Grandy, Thomas S. Scanlan, Elisabetta Cerbai, Riccardo Zucchi

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

3-iodothyronamine (T 1AM) is a novel endogenous relative of thyroid hormone, able to interact with trace amine-associated receptors, a class of plasma membrane G protein-coupled receptors, and to produce a negative inotropic and chronotropic effect. In the isolated rat heart 20-25 μM T 1AM decreased cardiac contractility, but oxygen consumption and glucose uptake were either unchanged or disproportionately high when compared to mechanical work. In adult rat cardiomyocytes acute exposure to 20 μM T 1AM decreased the amplitude and duration of the calcium transient. In patch clamped cardiomyocytes sarcolemmal calcium current density was unchanged while current facilitation by membrane depolarization was abolished consistent with reduced sarcoplasmic reticulum (SR) calcium release. In addition, T 1AM decreased transient outward current (I to) and I K1 background current. SR studies involving 20 μM T 1AM revealed a significant decrease in ryanodine binding due to reduced B max, no significant change in the rate constant of calcium-induced calcium release, a significant increase in calcium leak measured under conditions promoting channel closure, and no effect on oxalate-supported calcium uptake. Based on these observations we conclude T 1AM affects calcium and potassium homeostasis and suggest its negative inotropic action is due to a diminished pool of SR calcium as a result of increased diastolic leak through the ryanodine receptor, while increased action potential duration is accounted for by inhibition of I to and I K1 currents.

Original languageEnglish (US)
Pages (from-to)3082-3090
Number of pages9
JournalJournal of cellular and molecular medicine
Volume13
Issue number9 B
DOIs
StatePublished - Sep 1 2009

Keywords

  • 3-iodothyronamine
  • Calcium
  • Heart
  • Ionic current
  • Potassium
  • Ryanodine receptor
  • Sarcoplasmic reticulum
  • Thyroid

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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  • Cite this

    Ghelardoni, S., Suffredini, S., Frascarelli, S., Brogioni, S., Chiellini, G., Ronca-Testoni, S., Grandy, D. K., Scanlan, T. S., Cerbai, E., & Zucchi, R. (2009). Modulation of cardiac ionic homeostasis by 3-iodothyronamine. Journal of cellular and molecular medicine, 13(9 B), 3082-3090. https://doi.org/10.1111/j.1582-4934.2009.00728.x