β1 and β3 subunits amplify mechanosensitivity of the cardiac voltage-gated sodium channel Nav1.5

Maroni M, Körner J, Schüttler J, Winner B, Lampert A, Eberhardt E (2019)

Publication Language: English

Publication Type: Journal article

Publication year: 2019

Journal

Pflügers Archiv: European Journal of Physiology Springer

Book Volume: 471

Pages Range: 1481-1492

Journal Issue: 11-12

DOI: 10.1007/s00424-019-02324-w

Abstract

In cardiomyocytes, electrical activity is coupled to cellular contraction, thus exposing all proteins expressed in the sarcolemma to mechanical stress. The voltage-gated sodium channel Nav1.5 is the main contributor to the rising phase of the action potential in the heart. There is growing evidence that gating and kinetics of Nav1.5 are modulated by mechanical forces and pathogenic variants that affect mechanosensitivity have been linked to arrhythmias. Recently, the sodium channel β1 subunit has been described to stabilise gating against mechanical stress of Nav1.7 expressed in neurons. Here, we tested the effect of β1 and β3 subunits on mechanosensitivity of the cardiac Nav1.5. β1 amplifies stress-induced shifts of V1/2 of steady-state fast inactivation to hyperpolarised potentials (ΔV1/2: 6.2 mV without and 10.7 mV with β1 co-expression). β3, on the other hand, almost doubles stress-induced speeding of time to sodium current transient peak (Δtime to peak at − 30 mV: 0.19 ms without and 0.37 ms with β3 co-expression). Our findings may indicate that in cardiomyocytes, the interdependence of electrical activity and contraction is used as a means of fine tuning cardiac sodium channel function, allowing quicker but more strongly inactivating sodium currents under conditions of increased mechanical stress. This regulation may help to shorten action potential duration during tachycardia, to prevent re-entry phenomena and thus arrhythmias.

Authors with CRIS profile

Michele Maroni Department of Anaesthesiology Jürgen Schüttler Lehrstuhl für Anästhesiologie Beate Winner Professur für Stammzell-Modelle seltener neuraler Erkrankungen Esther Eberhardt Department of Anaesthesiology

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

IZKF-J66 (AN): ß subunits in human stem cell-derived nociceptors - adding pieces to the puzzle of pain Jan. 1, 2018 - Aug. 31, 2020

Involved external institutions

Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen DE Germany (DE)

How to cite

APA:

Maroni, M., Körner, J., Schüttler, J., Winner, B., Lampert, A., & Eberhardt, E. (2019). β1 and β3 subunits amplify mechanosensitivity of the cardiac voltage-gated sodium channel Nav1.5. Pflügers Archiv: European Journal of Physiology, 471(11-12), 1481-1492. https://doi.org/10.1007/s00424-019-02324-w

MLA:

Maroni, Michele, et al. "β1 and β3 subunits amplify mechanosensitivity of the cardiac voltage-gated sodium channel Nav1.5." Pflügers Archiv: European Journal of Physiology 471.11-12 (2019): 1481-1492.

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