Papers

Peer-reviewed Last author Corresponding author International journal
Aug, 2021

Differential effects of the formin inhibitor SMIFH2 on contractility and Ca2+ handling in frog and mouse cardiomyocytes

Genes to Cells
  • Koji Sakata, Sho Matsuyama, Nagomi Kurebayashi, Kengo Hayamizu, Takashi Murayama, Kunihide Nakamura, Kazuo Kitamura, Sachio Morimoto, Ryu Takeya

Volume
26
Number
8
First page
583
Last page
595
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1111/gtc.12873

Genetic mutations in actin regulators have been emerging as a cause of cardiomyopathy, although the functional link between actin dynamics and cardiac contraction remains largely unknown. To obtain insight into this issue, we examined the effects of pharmacological inhibition of formins, a major class of actin-assembling proteins. The formin inhibitor SMIFH2 significantly enhanced the cardiac contractility of isolated frog hearts, thereby augmenting cardiac performance. SMIFH2 treatment had no significant effects on the Ca2+ sensitivity of frog muscle fibers. Instead, it unexpectedly increased Ca2+ concentrations of isolated frog cardiomyocytes, suggesting that the inotropic effect is due to enhanced Ca2+ transients. In contrast to frog hearts, the contractility of mouse cardiomyocytes was attenuated by SMIFH2 treatment with decreasing Ca2+ transients. Thus, SMIFH2 has opposing effects on the Ca2+ transient and contractility between frog and mouse cardiomyocytes. We further found that SMIFH2 suppressed Ca2+ -release via type 2 ryanodine receptor (RyR2); this inhibitory effect may explain the species differences, since RyR2 is critical for Ca2+ transients in mouse myocardium but absent in frog myocardium. Although the mechanisms underlying the enhancement of Ca2+ transients in frog cardiomyocytes remain unclear, SMIFH2 differentially affects the cardiac contraction of amphibian and mammalian by differentially modulating their Ca2+ handling.

Link information
DOI
https://doi.org/10.1111/gtc.12873
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34060165
ID information
  • DOI : 10.1111/gtc.12873
  • Pubmed ID : 34060165

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