nNOS splice variants differentially regulate myofilament function but are dispensable for intracellular calcium and force transients in cardiac papillary muscles

PloS One
W Glenn L KerrickJustin M Percival

Abstract

Cardiac muscle expresses three neuronal nitric oxide synthase (nNOS) splice variants: nNOSα, nNOSμ and nNOSβ. The functions of these nNOS splice variants in cardiac muscle, particularly myofilament-associated nNOSβ are unclear. To decipher cardiac nNOS splice variant function we investigated myofilament function and intracellular calcium and force transients in demembranated and intact papillary muscles from two lines of nNOS knockout mice. The first line (KN1) lacks nNOSα and nNOSμ. The second line (KN2) lacks active nNOSα, nNOSμ and nNOSβ. Demembranated KN1 papillary muscles exhibited reduced myofilament ATPase activity (-35%) and specific force (-10%) relative to controls. Demembranated KN2 muscles exhibited a smaller decrease in myofilament ATPase activity (-21%), but a greater reduction in specific force (-26%) relative to controls. Myofilament calcium sensitivity in demembranated KN1 and KN2 papillary muscles was similar to controls. Thus, papillary muscle-expressed nNOS splice variants are necessary for control levels of myofilament ATPase activity and force generation, but dispensable for myofilament calcium sensitivity. The greater reduction in myofilament ATPase relative to specific force in KN1, but not KN2 muscle, r...Continue Reading

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Citations

Aug 3, 2020·Reviews in the Neurosciences·Masoumeh Kourosh-AramiMohammad Taghi Joghataei

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Software Mentioned

Guth Muscle Research System
Prism
Graphpad

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