Force development and intracellular Ca2+ in intact cardiac muscles from gravin mutant mice

Zhitao Li, Sonal Singh, Santosh V. Suryavanshi, Wengang Ding, Xiaoxu Shen, Cori S. Wijaya, Wei Dong Gao, Bradley K. McConnell

Research output: Contribution to journalArticlepeer-review


Gravin (AKAP12) is an A-kinase-anchoring-protein that scaffolds protein kinase A (PKA), β2-adrenergic receptor (β2-AR), protein phosphatase 2B and protein kinase C. Gravin facilitates β2-AR-dependent signal transduction through PKA to modulate cardiac excitation-contraction coupling and its removal positively affects cardiac contraction. Trabeculae from the right ventricles of gravin mutant (gravin-t/t) mice were employed for force determination. Simultaneously, corresponding intracellular Ca2+ transient ([Ca2+]i) were measured. Twitch force (Tf)-interval relationship, [Ca2+]i-interval relationship, and the rate of decay of post-extrasysolic potentiation (Rf) were also obtained. Western blot analysis were performed to correlate sarcomeric protein expression with alterations in calcium cycling between the WT and gravin-t/t hearts. Gravin-t/t muscles had similar developed force compared to WT muscles despite having lower [Ca2+]i at any given external Ca2+ concentration ([Ca2+]o). The time to peak force and peak [Ca2+]i were slower and the time to 75% relaxation was significantly prolonged in gravin-t/t muscles. Both Tf-interval and [Ca2+]i-interval relations were depressed in gravin-t/t muscles. Rf, however, did not change. Furthermore, Western blot analysis revealed decreased ryanodine receptor (RyR2) phosphorylation in gravin-t/t hearts. Gravin-t/t cardiac muscle exhibits increased force development in responsiveness to Ca2+. The Ca2+ cycling across the SR appears to be unaltered in gravin-t/t muscle. Our study suggests that gravin is an important component of cardiac contraction regulation via increasing myofilament sensitivity to calcium. Further elucidation of the mechanism can provide insights to role of gravin if any in the pathophysiology of impaired contractility.

Original languageEnglish (US)
Pages (from-to)117-126
Number of pages10
JournalEuropean Journal of Pharmacology
StatePublished - 2017


  • Cardiac muscle
  • Contraction
  • Force development
  • Gravin
  • Intracellular calcium
  • Trabeculae

ASJC Scopus subject areas

  • Pharmacology


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