NO-sGC pathway modulates Ca2+ release and muscle contraction in zebrafish skeletal muscle

• Verfasst von: Zhou, Xiyuan [VerfasserIn]
• Verfasst von: Fink, Rainer [VerfasserIn]
• Verfasst von: Mosqueira, Matias [VerfasserIn]
• Titel: NO-sGC pathway modulates Ca2+ release and muscle contraction in zebrafish skeletal muscle
• Verf.angabe: Zhou Xiyuan, Rainer H.A. Fink and Matias Mosqueira
• E-Jahr: 2017
• Jahr: 23 August 2017
• Umfang: 15 S.
• Fussnoten: Im Titel ist "2+" hochgestellt ; Gesehen am 06.08.2018
• Titel Quelle: Enthalten in: Frontiers in physiology
• Ort Quelle: Lausanne : Frontiers Research Foundation, 2007
• Jahr Quelle: 2017
• Band/Heft Quelle: 8(2017) Artikel-Nummer 607, 15 Seiten
• ISSN Quelle: 1664-042X
• DOI: doi:10.3389/fphys.2017.00607
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: : skeletal muscle
• Sach-SW: Calcium transient
• Sach-SW: force
• Sach-SW: Nitric Oxide
• Sach-SW: Zebrafish
• K10plus-PPN: 1578299810

Abstract

Vertebrate skeletal muscle contraction and relaxation is a complex process that depends on Ca2+ ions to promote the interaction of actin and myosin. This process can be modulated by nitric oxide (NO), a gas molecule synthesized endogenously by (nitric oxide synthase) NOS isoforms. At nanomolar concentrations NO activates soluble guanylate cyclase (sGC), which in turn activates protein kinase G via conversion of GTP into cyclic GMP. Alternatively, NO post-translationally modifies proteins via S-nitrosylation of the thiol group of cysteine. However, the mechanisms of action of NO on Ca2+ homeostasis during muscle contraction are not fully understood and we hypothesize that NO exerts its effects on Ca2+ homeostasis in skeletal muscles mainly through negative modulation of Ca2+ release and Ca2+ uptake via the NO-sGC-PKG pathway. To address this, we used 5-7 days-post fecundation-larvae of zebrafish, a well-established animal model for physiological and pathophysiological muscle activity. We evaluated the response of muscle contraction and Ca2+ transients in presence of SNAP, a NO-donor or L-NAME, an unspecific NOS blocker in combination with specific blockers of key proteins of Ca2+ homeostasis. We also evaluate the expression of NOS in combination with dihydropteridine receptor, ryanodine receptor and sarco/endoplasmic reticulum Ca2+ ATPase. We concluded that endogenous NO reduced force production through negative modulation of Ca2+ transients via the NO-sGC pathway. This effect could be reversed using an unspecific NOS blocker or sGC blocker.