Chamber-specific regulation of myofilament Ca2+ sensitivity by nNOSβ via troponin I phosphorylation: Predominance in the right ventricle.

Authors

Jae Won Kwon, Hyerim Park, Ryeon Heo, Jihyun Jang, Jintae Kim, Seung Beom Oh, Yin Hua Zhang, Sung Joon Kim, Young Keul Jeon

Published in

The Journal of general physiology. Volume 158. Issue 6. Nov 02, 2026. Epub Oct 05, 2026.

Abstract

Neuronal nitric oxide (NO) synthase (nNOS) is an important regulator of excitation-contraction coupling in cardiomyocytes, yet its chamber-specific role in right ventricular cardiomyocytes (RVCMs) remains incompletely understood. In this study, we compared the effects of nNOS inhibition on contractile function, Ca2+ signaling, and myofilament-associated regulation in RVCMs and left ventricular cardiomyocytes (LVCMs). Pharmacological inhibition of nNOS with S-methyl-L-thiocitrulline (SMTC) enhanced sarcomere shortening and impaired relaxation in both cell types, with markedly greater effects observed in RVCMs. In contrast, SMTC-induced changes in Ca2+ transients and L-type Ca2+ current were more pronounced in LVCMs than in RVCMs, indicating a dissociation between Ca2+ signaling and mechanical responses in the SMTC-treated RVCMs. Analysis of dynamic Ca2+-sarcomere length coupling indicated that nNOS inhibition in RVCMs preferentially altered the relationship between intracellular Ca2+ signaling and sarcomere response, particularly during relaxation, rather than simply reflecting changes in Ca2+ magnitude. Consistent with this interpretation, inhibition of nNOS reduced cardiac troponin I (cTnI) Ser23/24 phosphorylation and was associated with altered endogenous Ca2+ buffering properties in RVCMs. Moreover, myofilament-enriched fractions from RVCMs exhibited higher levels of Ser1417-phosphorylated nNOSβ. Collectively, these data indicate that myofilament-associated nNOSβ predominantly regulates RV contractility through cTnI phosphorylation-mediated Ca2+ desensitization.

PMID:
42831835
Bibliographic data and abstract were imported from PubMed on 05 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.