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Emergence of Orai3 activity during cardiac hypertrophy

Youakim Saliba1, Mathilde Keck2, Alexandre Marchand2

  • 1Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1166, ICAN, F-75005 Paris, France INSERM, UMR_S 1166, ICAN, F-75005 Paris, France Laboratoire de Recherche en Physiologie et Physiopathologie, Pôle Technologie Santé, Faculté de Médecine, Université Saint Joseph, Beyrouth, Lebanon.

Cardiovascular Research
|September 13, 2014
PubMed

Insights

Stromal interaction molecule 1 (STIM1) interacts with Orai3 to control calcium influx in adult cardiomyocytes, particularly during hypertrophy. Orai3 is key for store-independent calcium entry and arachidonic acid-activated currents.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Calcium Signaling

Background:

  • Stromal interaction molecule 1 (STIM1) regulates calcium (Ca2+) influx in cardiomyocytes during hypertrophy.
  • The roles of Orai1 and Orai3 in STIM1-dependent calcium influx in cardiomyocytes are not fully understood.

Purpose of the Study:

  • To investigate the interaction between Orai1, Orai3, and STIM1.
  • To determine the role of Orai1 and Orai3 in store-independent and store-operated Ca2+ influx in cardiomyocytes.

Main Methods:

  • Characterized Orai protein expression and STIM1 interaction in normal and hypertrophied cardiomyocytes.
  • Utilized in vivo siRNA delivery to silence Orai channels in adult ventricular cardiomyocytes.
  • Measured voltage-independent Ca2+ entries and Orai-mediated currents using Fura-2 AM and patch-clamp techniques.

Main Results:

  • Orai1 and Orai3 protein levels were unchanged during hypertrophy, but both co-immunoprecipitated with STIM1.
  • Orai3, not Orai1, was identified as the critical STIM1 partner for voltage-independent Ca2+ entry in hypertrophied cardiomyocytes.
  • Orai3 mediated arachidonic acid-activated inward currents.

Conclusions:

  • Cardiac Orai3 is essential for STIM1-mediated voltage-independent Ca2+ entry in adult cardiomyocytes.
  • Arachidonic acid-activated currents, supported by Orai3, are present and increased during cardiac hypertrophy.
Abstract

Keywords:
CalciumCardiac hypertrophyOraiSTIM1SiRNA

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