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Arrhythmogenic calmodulin mutations disrupt intracellular cardiomyocyte Ca2+ regulation by distinct mechanisms.

Yin G, Hassan F, Haroun AR, Murphy LL, Crotti L, Schwartz PJ, George AL, Satin J - J Am Heart Assoc (2014)

Bottom Line: LQTS-CaM mutants do not consistently affect L-type Na current in heterologous cells or native cardiomyocytes, suggesting that the Na channel does not contribute to LQTS pathogenesis in the context of CaM mutations.LQTS-CaM mutants led to loss of Ca2+-transient entrainment with the rank order from greatest to least effect: CaM-D130G~CaM-D96V>CaM-F142L.CaM mutations associated with LQTS may not affect L-type Na+ current but may evoke defective Ca2+-dependent inactivation of L-type Ca2+ current.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Kentucky College of Medicine, Lexington, KY (G.Y., F.H., A.R.H., J.S.).

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Catecholaminergic polymorphic ventricular tachycardia calmodulin induces abnormal Ca2+ transients. A, Representative Ca2+ transients in cardiomyocytes expressing calmodulin‐N54I. B, Loss of entrainment for frequencies ≥1 Hz; for 3 Hz, no entrainment was possible. P<10−4. C, Representative Ca2+ transient displaying alternans at 1 Hz. D, For 1 Hz, all calmodulin‐N54I cardiomyocytes displayed abnormal Ca2+‐transient phenotypes; the majority of cells displayed alternans. P<10−4. WT indicates wild type.
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fig07: Catecholaminergic polymorphic ventricular tachycardia calmodulin induces abnormal Ca2+ transients. A, Representative Ca2+ transients in cardiomyocytes expressing calmodulin‐N54I. B, Loss of entrainment for frequencies ≥1 Hz; for 3 Hz, no entrainment was possible. P<10−4. C, Representative Ca2+ transient displaying alternans at 1 Hz. D, For 1 Hz, all calmodulin‐N54I cardiomyocytes displayed abnormal Ca2+‐transient phenotypes; the majority of cells displayed alternans. P<10−4. WT indicates wild type.

Mentions: Data were analyzed for Figures 5C, 6B, 7B, and 7D with the chi‐square test. Figure 9A was analyzed with 1‐way ANOVA with Dunn's multiple comparison test. Figure 9A and the remaining data analysis passed the D'Agostino and Pearson test and the Shapiro‐Wilk test for normality, and tests of statistical difference for the remaining data were performed using the t test with statistical significance correction of multiple comparisons and α=0.05 using the Holm‐Sidak method in GraphPad Prism version 6.0 for Windows (GraphPad Software, La Jolla, CA).


Arrhythmogenic calmodulin mutations disrupt intracellular cardiomyocyte Ca2+ regulation by distinct mechanisms.

Yin G, Hassan F, Haroun AR, Murphy LL, Crotti L, Schwartz PJ, George AL, Satin J - J Am Heart Assoc (2014)

Catecholaminergic polymorphic ventricular tachycardia calmodulin induces abnormal Ca2+ transients. A, Representative Ca2+ transients in cardiomyocytes expressing calmodulin‐N54I. B, Loss of entrainment for frequencies ≥1 Hz; for 3 Hz, no entrainment was possible. P<10−4. C, Representative Ca2+ transient displaying alternans at 1 Hz. D, For 1 Hz, all calmodulin‐N54I cardiomyocytes displayed abnormal Ca2+‐transient phenotypes; the majority of cells displayed alternans. P<10−4. WT indicates wild type.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4309107&req=5

fig07: Catecholaminergic polymorphic ventricular tachycardia calmodulin induces abnormal Ca2+ transients. A, Representative Ca2+ transients in cardiomyocytes expressing calmodulin‐N54I. B, Loss of entrainment for frequencies ≥1 Hz; for 3 Hz, no entrainment was possible. P<10−4. C, Representative Ca2+ transient displaying alternans at 1 Hz. D, For 1 Hz, all calmodulin‐N54I cardiomyocytes displayed abnormal Ca2+‐transient phenotypes; the majority of cells displayed alternans. P<10−4. WT indicates wild type.
Mentions: Data were analyzed for Figures 5C, 6B, 7B, and 7D with the chi‐square test. Figure 9A was analyzed with 1‐way ANOVA with Dunn's multiple comparison test. Figure 9A and the remaining data analysis passed the D'Agostino and Pearson test and the Shapiro‐Wilk test for normality, and tests of statistical difference for the remaining data were performed using the t test with statistical significance correction of multiple comparisons and α=0.05 using the Holm‐Sidak method in GraphPad Prism version 6.0 for Windows (GraphPad Software, La Jolla, CA).

Bottom Line: LQTS-CaM mutants do not consistently affect L-type Na current in heterologous cells or native cardiomyocytes, suggesting that the Na channel does not contribute to LQTS pathogenesis in the context of CaM mutations.LQTS-CaM mutants led to loss of Ca2+-transient entrainment with the rank order from greatest to least effect: CaM-D130G~CaM-D96V>CaM-F142L.CaM mutations associated with LQTS may not affect L-type Na+ current but may evoke defective Ca2+-dependent inactivation of L-type Ca2+ current.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Kentucky College of Medicine, Lexington, KY (G.Y., F.H., A.R.H., J.S.).

Show MeSH
Related in: MedlinePlus