CaV1.3 L-type Ca2+ channel contributes to the heartbeat by generating a dihydropyridine-sensitive persistent Na+ current - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2017

CaV1.3 L-type Ca2+ channel contributes to the heartbeat by generating a dihydropyridine-sensitive persistent Na+ current

Résumé

The spontaneous activity of sinoatrial node (SAN) pacemaker cells is generated by a functional interplay between the activity of ionic currents of the plasma membrane and intracellular Ca2+ dynamics. The molecular correlate of a dihydropyridine (DHP)-sensitive sustained inward Na+ current (I st), a key player in SAN automaticity, is still unknown. Here we show that I st and the L-type Ca2+ current (I Ca,L) share CaV1.3 as a common molecular determinant. Patch-clamp recordings of mouse SAN cells showed that I st is activated in the diastolic depolarization range, and displays Na+ permeability and minimal inactivation and sensitivity to I Ca,L activators and blockers. Both CaV1.3-mediated I Ca,L and I st were abolished in CaV1.3-deficient (CaV1.3-/-) SAN cells but the CaV1.2-mediated I Ca,L current component was preserved. In SAN cells isolated from mice expressing DHP-insensitive CaV1.2 channels (CaV1.2DHP-/-), I st and CaV1.3-mediated I Ca,L displayed overlapping sensitivity and concentration-response relationships to the DHP blocker nifedipine. Consistent with the hypothesis that CaV1.3 rather than CaV1.2 underlies I st, a considerable fraction of I Ca,L was resistant to nifedipine inhibition in CaV1.2DHP-/- SAN cells. These findings identify CaV1.3 channels as essential molecular components of the voltage-dependent, DHP-sensitive I st Na+ current in the SAN.

Domaines

Biologie animale
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Origine : Publication financée par une institution

Dates et versions

hal-01778161 , version 1 (27-05-2021)

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Paternité

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Futoshi Toyoda, Pietro Mesirca, Stefan Dübel, Wei-Guang Ding, Joerg Striessnig, et al.. CaV1.3 L-type Ca2+ channel contributes to the heartbeat by generating a dihydropyridine-sensitive persistent Na+ current. Scientific Reports, 2017, 7 (1), pp.7869. ⟨10.1038/s41598-017-08191-8⟩. ⟨hal-01778161⟩
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