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Journal of Interventional Cardiac Electrophysiology

Published in:

01-10-2009

Lack of gelsolin promotes perpetuation of atrial fibrillation in the mouse heart

Authors: Jan Wilko Schrickel, Klaus Fink, Rainer Meyer, Christian Grohé, Florian Stoeckigt, Klaus Tiemann, Alexander Ghanem, Lars Lickfett, Georg Nickenig, Thorsten Lewalter

Published in: Journal of Interventional Cardiac Electrophysiology | Issue 1/2009

Abstract

Purpose

Gelsolin (gsn) is involved in the reorganization of the cytoskeleton, thereby modulating cardiomyocytal L-type Ca²⁺ channels. We investigated global cardiac electrophysiological characteristics in a gsn-deficient (gsn^−/−) mouse strain.

Methods

Using transvenous catheterization, atrial and ventricular stimulation were performed in 15 male mice [eight gsn^−/−, seven wild-type (gsn^+/+)]. Surface ECG, standard electrophysiological parameters, and inducibility of atrial fibrillation (AF) were evaluated.

Results

The surface ECG showed shorter PQ (37.8 ± 4.6 versus 42.9 ± 2.7 ms; P = 0.02), but longer QRS (16.5 ± 1.8 versus 13.9 ± 1.2 ms; P = 0.005) and QT intervals (38.5 ± 2.2 versus 35.6 ± 2.4 ms, P = 0.03) in gsn^−/−. Gsn^−/− exhibited significantly higher susceptibility to induction of prolonged AF episodes ≥60 s [six of eight gsn^−/− versus one of seven gsn^+/+; P = 0.04]. Sustained AF episodes ≥10 min were observed in 50% of the gsn-deficient animals.

Conclusions

Gsn deficiency results in perpetuation of inducible episodes of atrial fibrillation. Altered L-type Ca²⁺ currents and disturbed Ca²⁺ handling known to be associated to gsn deficiency likely contribute to this effect.

Yin, H. L. (1987). Gelsolin: Calcium- and polyphosphoinositide-regulated actin-modulating protein. Bioessays, 7, 176–179.PubMedCrossRef

Khaitlina, S., & Hinssen, H. (1997). Conformational changes in actin induced by its interaction with gelsolin. Biophys J, 73, 929–937.PubMedCrossRef

Furukawa, K., Fu, W., Li, Y., Witke, W., Kwiatkowski, D. J., & Mattson, M. P. (1997). The actin-severing protein gelsolin modulates calcium channel and NMDA receptor activities and vulnerability to excitotoxicity in hippocampal neurons. J Neurosci, 17, 8178–8186.PubMed

Kinosian, H. J., Newman, J., Lincoln, B., Selden, L. A., Gershman, L. C., & Estes, J. E. (1998). Ca2+ regulation of gelsolin activity: binding and severing of F-actin. Biophys J, 75, 3101–3109.PubMedCrossRef

Zapun, A., Grammatyka, S., Deral, G., & Vernet, T. (2000). Calcium-dependent conformational stability of modules 1 and 2 of human gelsolin. Biochem J, 350(Pt 3), 873–881.PubMedCrossRef

Endres, M., Fink, K., Zhu, J., Stagliano, N. E., Bondada, V., Geddes, J. W., et al. (1999). Neuroprotective effects of gelsolin during murine stroke. J Clin Invest, 103, 347–354.PubMedCrossRef

Lader, A. S., Kwiatkowski, D. J., & Cantiello, H. F. (1999). Role of gelsolin in the actin filament regulation of cardiac L-type calcium channels. Am J Physiol, 277, C1277–C1283.PubMed

Yang, J., Moravec, C. S., Sussman, M. A., DiPaola, N. R., Fu, D., Hawthorn, L., et al. (2000). Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays. Circulation, 102, 3046–3052.PubMed

Witke, W., Sharpe, A. H., Hartwig, J. H., Azuma, T., Stossel, T. P., & Kwiatkowski, D. J. (1995). Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolin. Cell, 81, 41–51.PubMedCrossRef

10.

Grohe, C., Kann, S., Fink, L., Djoufack, P. C., Paehr, M., van Eickels, M., et al. (2004). 17 Beta-estradiol regulates nNOS and eNOS activity in the hippocampus. Neuroreport, 15, 89–93.PubMedCrossRef

11.

Kreuzberg, M. M., Schrickel, J. W., Ghanem, A., Kim, J. S., Degen, J., Janssen-Bienhold, U., et al. (2006). Connexin30.2 containing gap junction channels decelerate impulse propagation through the atrioventricular node. Proc Natl Acad Sci USA, 103, 5959–5964.PubMedCrossRef

12.

Schrickel, J. W., Brixius, K., Herr, C., Clemen, C. S., Sasse, P., Reetz, K., et al. (2007). Enhanced heterogeneity of myocardial conduction and severe cardiac electrical instability in annexin A7-deficient mice. Cardiovasc Res, 76, 257–268.PubMedCrossRef

13.

Mitchell, G. F., Jeron, A., & Koren, G. (1998). Measurement of heart rate and Q-T interval in the conscious mouse. Am J Physiol, 274, H747–H751.PubMed

14.

Schrickel, J. W., Bielik, H., Yang, A., Schimpf, R., Shlevkov, N., Burkhardt, D., et al. (2002). Induction of atrial fibrillation in mice by rapid transesophageal atrial pacing. Basic Res Cardiol, 97, 452–460.PubMedCrossRef

15.

Hagendorff, A., Schumacher, B., Kirchhoff, S., Luderitz, B., & Willecke, K. (1999). Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation. Circulation, 99, 1508–1515.PubMed

16.

Calaghan, S. C., Le Guennec, J. Y., & White, E. (2004). Cytoskeletal modulation of electrical and mechanical activity in cardiac myocytes. Prog Biophys Mol Biol, 84, 29–59.PubMedCrossRef

17.

Silacci, P., Mazzolai, L., Gauci, C., Stergiopulos, N., Yin, H. L., & Hayoz, D. (2004). Gelsolin superfamily proteins: key regulators of cellular functions. Cell Mol Life Sci, 61, 2614–2623.PubMedCrossRef

18.

Stendahl, O., Krause, K. H., Krischer, J., Jerstrom, P., Theler, J. M., Clark, R. A., et al. (1994). Redistribution of intracellular Ca2+ stores during phagocytosis in human neutrophils. Science, 265, 1439–1441.PubMedCrossRef

19.

Lai, L. P., Su, M. J., Lin, J. L., Lin, F. Y., Tsai, C. H., Chen, Y. S., et al. (1999). Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca(2+)-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban: an insight into the mechanism of atrial electrical remodeling. J Am Coll Cardiol, 33, 1231–1237.PubMedCrossRef

20.

Van Wagoner, D. R., & Nerbonne, J. M. (2000). Molecular basis of electrical remodeling in atrial fibrillation. J Mol Cell Cardiol, 32, 1101–1117.PubMedCrossRef

21.

Van Wagoner, D. R., Pond, A. L., Lamorgese, M., Rossie, S. S., McCarthy, P. M., & Nerbonne, J. M. (1999). Atrial L-type Ca2+ currents and human atrial fibrillation. Circ Res, 85, 428–436.PubMed

22.

Skasa, M., Jungling, E., Picht, E., Schondube, F., & Luckhoff, A. (2001). L-type calcium currents in atrial myocytes from patients with persistent and non-persistent atrial fibrillation. Basic Res Cardiol, 96, 151–159.PubMedCrossRef

23.

van der Velden, H. M. W., van der Zee, L., Wijffels, M. C., van Leuven, C., Dorland, R., Vos, M. A., et al. (2000). Atrial fibrillation in the goat induces changes in monophasic action potential and mRNA expression of ion channels involved in repolarization. J Cardiovasc Electrophysiol, 11, 1262–1269.PubMedCrossRef

24.

Klein, G., Schroder, F., Vogler, D., Schaefer, A., Haverich, A., Schieffer, B., et al. (2003). Increased open probability of single cardiac L-type calcium channels in patients with chronic atrial fibrillation. Role of phosphatase 2A. Cardiovasc Res, 59, 37–45.PubMedCrossRef

Title: Lack of gelsolin promotes perpetuation of atrial fibrillation in the mouse heart
Authors: Jan Wilko Schrickel
Klaus Fink
Rainer Meyer
Christian Grohé
Florian Stoeckigt
Klaus Tiemann
Alexander Ghanem
Lars Lickfett
Georg Nickenig
Thorsten Lewalter
Publication date: 01-10-2009
Publisher: Springer US
Published in: Journal of Interventional Cardiac Electrophysiology / Issue 1/2009
Print ISSN: 1383-875X
Electronic ISSN: 1572-8595
DOI: https://doi.org/10.1007/s10840-009-9425-4

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Lack of gelsolin promotes perpetuation of atrial fibrillation in the mouse heart

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Purpose

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