التفاصيل البيبلوغرافية
| العنوان: |
Striatin knock out induces a gain of function of INa and impaired Ca2+ handling in mESC‐derived cardiomyocytes. |
| المؤلفون: |
Benzoni, P., Arici, M., Giannetti, F., Cospito, A., Prevostini, R., Volani, C., Fassina, L., Rosato‐Siri, M. D., Metallo, A., Gennaccaro, L., Suffredini, S., Foco, L., Mazzetti, S., Calogero, A., Cappelletti, G., Leibbrandt, A., Elling, U., Broso, F., Penninger, J. M., Pramstaller, P. P. |
| المصدر: |
Acta Physiologica; Aug2024, Vol. 240 Issue 8, p1-16, 16p |
| مصطلحات موضوعية: |
ACTION potentials, EMBRYONIC stem cells, SCAFFOLD proteins, CELL membranes, HEART diseases |
| مستخلص: |
Aim: Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its pathogenicity have been poorly investigated. Methods: We studied the role(s) of cardiac Strn gene (STRN) by comparing the functional properties of CMs, generated from Strn‐KO and isogenic WT mouse embryonic stem cell lines. Results: The spontaneous beating rate of Strn‐KO CMs was faster than WT cells, and this correlated with a larger fast INa conductance and no changes in If. Paced (2–8 Hz) Strn‐KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in ICaL and IKr. Motion video tracking analysis highlighted an altered contraction in Strn‐KO CMs; this was associated with a global increase in intracellular Ca2+, caused by an enhanced late Na+ current density (INaL) and a reduced Na+/Ca2+ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na+ channel expression and a more dynamic microtubule network in Strn‐KO CMs than in WT. Indeed, incubation of Strn‐KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of INa conductance toward WT levels. Conclusion: Loss of STRN alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn‐related multi‐protein complexes. This leads to impaired microtubules dynamics and Na+ channels trafficking to the plasma membrane, causing a global Na+ and Ca2+ enhancement. [ABSTRACT FROM AUTHOR] |
|
Copyright of Acta Physiologica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder