Calcium-dependent inactivation controls cardiac L-type Ca2+ currents under β-adrenergic stimulation

The Journal of General Physiology
Danna MoralesDiego Varela

Abstract

The activity of L-type calcium channels is associated with the duration of the plateau phase of the cardiac action potential (AP) and it is controlled by voltage- and calcium-dependent inactivation (VDI and CDI, respectively). During β-adrenergic stimulation, an increase in the L-type current and parallel changes in VDI and CDI are observed during square pulses stimulation; however, how these modifications impact calcium currents during an AP remains controversial. Here, we examined the role of both inactivation processes on the L-type calcium current activity in newborn rat cardiomyocytes in control conditions and after stimulation with the β-adrenergic agonist isoproterenol. Our approach combines a self-AP clamp (sAP-Clamp) with the independent inhibition of VDI or CDI (by overexpressing CaVβ2a or calmodulin mutants, respectively) to directly record the L-type calcium current during the cardiac AP. We find that at room temperature (20-23°C) and in the absence of β-adrenergic stimulation, the L-type current recapitulates the AP kinetics. Furthermore, under our experimental setting, the activity of the sodium-calcium exchanger (NCX) does not affect the shape of the AP. We find that hindering either VDI or CDI prolongs the L-typ...Continue Reading

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Citations

Apr 21, 2019·The Journal of General Physiology·Maedeh Bazmi, Ariel L Escobar
Sep 4, 2020·Investigative Ophthalmology & Visual Science·Soufien SghariLena Gunhaga
Jul 17, 2021·The Journal of General Physiology·Brooke M AhernJonathan Satin
Jul 17, 2021·Channels·Ahmet Kürşad Sırcan, Sevgi Şengül Ayan

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Methods Mentioned

BETA
transfection

Software Mentioned

MATLAB
Clamp
Clampfit
sAP
SigmaPlot

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