Effects of endogenous cannabinoid anandamide on cardiac Na+/Ca2+ exchanger

Lina T.Al Kury, Keun Hang Susan Yang, Faisal T. Thayyullathil, Mohanraj Rajesh, Ramez M. Ali, Yaroslav M. Shuba, Frank Christopher Howarth, Sehamuddin Galadari, Murat Oz

Research output: Contribution to journalArticlepeer-review

Abstract

Endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) has been shown to cause negative inotropic and antiarrhythmic effects in ventricular myocytes. In this study, using whole-cell patch clamp technique, we have investigated the effects of AEA on cardiac Na+/Ca2+ exchanger (NCX1)-mediated currents. AEA suppressed NCX1 with an IC50 value of 4.7μM. Both inward and outward components of exchanger currents were suppressed by AEA equally. AEA inhibition was mimicked by the metabolically stable analogue, methanandamide (metAEA, 10μM) while it was not influenced by inhibition of fatty acid amide hydrolase with 1μM URB597 incubation. The effect of AEA, was not altered in the presence of cannabinoid receptor 1 and 2 antagonists AM251 (1μM) and AM630 (1μM), respectively. In addition, inhibition by AEA remained unchanged after pertussis toxin (PTX, 2μg/ml) treatment or following the inclusion of GDP-β-S (1mM) in pipette solution. Currents mediated by NCX1 expressed in HEK-293cells were also inhibited by 10μM AEA a partially reversible manner. Confocal microscopy images indicated that the intensity of YFP-NCX1 expression on cell surface was not altered by AEA. Collectively, the results indicate that AEA directly inhibits the function of NCX1 in rat ventricular myocytes and in HEK-293cells expressing NCX1.

Original languageEnglish (US)
Pages (from-to)231-237
Number of pages7
JournalCell Calcium
Volume55
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • Anandamide
  • Whole-cell patch clamp technique

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Effects of endogenous cannabinoid anandamide on cardiac Na<sup>+</sup>/Ca<sup>2+</sup> exchanger'. Together they form a unique fingerprint.

Cite this