English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

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 Ca 2+  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 Ca 2+  current ( I   Ca,L ) share Ca V 1.3 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 Ca V 1.3-mediated  I   Ca,L  and  I   st  were abolished in Ca V 1.3-deficient (Ca V 1.3 −/− ) SAN cells but the Ca V 1.2-mediated  I   Ca,L  current component was preserved. In SAN cells isolated from mice expressing DHP-insensitive Ca V 1.2 channels (Ca V 1.2 DHP−/− ),  I   st  and Ca V 1.3-mediated  I   Ca,L  displayed overlapping sensitivity and concentration–response relationships to the DHP blocker nifedipine. Consistent with the hypothesis that Ca V 1.3 rather than Ca V 1.2 underlies  I   st , a considerable fraction of  I   Ca,L  was resistant to nifedipine inhibition in Ca V 1.2 DHP−/−  SAN cells. These findings identify Ca V 1.3 channels as essential molecular components of the voltage-dependent, DHP-sensitive  I   st  Na +  current in the SAN.

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