title: Irisin evokes bradycardia by activating cardiac-projecting neurons of nucleus ambiguus.
abstract: Irisin is a newly identified hormone induced in muscle and adipose tissues by physical activity. This protein and its encoding gene have been identified in the brain; in addition, the precursor for irisin, FNDC5, can cross the blood-brain barrier. The fact that irisin is secreted during exercise together with the lower resting heart rate in athletes prompted us to investigate the effect of irisin on cardiac-projecting vagal neurons of nucleus ambiguus, a key regulatory site of heart rate. In vitro experiments in cultured nucleus ambiguus neurons indicate that irisin activates these neurons, inducing an increase in cytosolic Ca(2+) concentration and neuronal depolarization. In vivo microinjection of irisin into the nucleus ambiguus promotes bradycardia in conscious rats. Our study is the first to report the effects of irisin on the neurons controlling the cardiac vagal tone and to link a myokine to a cardioprotective role, by modulating central cardiovascular regulation.
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Eugen
authors.initials: E
authors.lastname: Brailoiu
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Elena
authors.initials: E
authors.lastname: Deliu
authors.affiliation: Department of Internal Medicine, Brandywine Hospital, Coatesville, Pennsylvania.
authors.forename: Romeo A
authors.initials: RA
authors.lastname: Sporici
authors.affiliation: Department of Pharmaceutical Sciences, Jefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, Pennsylvania gcb004@jefferson.edu.
authors.forename: G Cristina
authors.initials: GC
authors.lastname: Brailoiu
keywords: Autonomic cardiovascular regulation; cytosolic Ca2+; membrane potential; vagal tone