Fluvoxamine rescues mitochondrial Ca2+ transport and ATP production through σ1-receptor in hypertrophic cardiomyocytes
2014
Tagashira, Hideaki | Bhuiyan, Md Shenuarin | Shioda, Norifumi | Fukunaga, Kohji
We previously reported that fluvoxamine, a selective serotonin reuptake inhibitor with high affinity for the σ1-receptor (σ1R), ameliorates cardiac hypertrophy and dysfunction via σ1R stimulation. Although σ1R on non-cardiomyocytes interacts with the IP3 receptor (IP3R) to promote mitochondrial Ca²⁺ transport, little is known about its physiological and pathological relevance in cardiomyocytes.Here we performed Ca²⁺ imaging and measured ATP production to define the role of σ1Rs in regulating sarcoplasmic reticulum (SR)-mitochondrial Ca²⁺ transport in neonatal rat ventricular cardiomyocytes treated with angiotensin II to promote hypertrophy.These cardiomyocytes exhibited imbalances in expression levels of σ1R and IP3R and impairments in both phenylephrine-induced mitochondrial Ca²⁺ mobilization from the SR and ATP production. Interestingly, σ1R stimulation with fluvoxamine rescued impaired mitochondrial Ca²⁺ mobilization and ATP production, an effect abolished by treatment of cells with the σ1R antagonist, NE-100. Under physiological conditions, fluvoxamine stimulation of σ1Rs suppressed intracellular Ca²⁺ mobilization through IP3Rs and ryanodine receptors (RyRs). In vivo, chronic administration of fluvoxamine to TAC mice also rescued impaired ATP production.These results suggest that σ1R stimulation with fluvoxamine promotes SR-mitochondrial Ca²⁺ transport and mitochondrial ATP production, whereas σ1R stimulation suppresses intracellular Ca²⁺ overload through IP3Rs and RyRs. These mechanisms likely underlie in part the anti-hypertrophic and cardioprotective action of the σ1R agonists including fluvoxamine.
Afficher plus [+] Moins [-]Mots clés AGROVOC
Informations bibliographiques
Cette notice bibliographique a été fournie par National Agricultural Library
Découvrez la collection de ce fournisseur de données dans AGRIS