L-type Cav1.3 channels regulate ryanodine receptor-dependent Ca2+ release during sino-atrial node pacemaker activity

Cardiovascular Research
Angelo G TorrenteMatteo E Mangoni

Abstract

Sino-atrial node (SAN) automaticity is an essential mechanism of heart rate generation that is still not completely understood. Recent studies highlighted the importance of intracellular Ca(2+) ([Ca(2+)]i) dynamics during SAN pacemaker activity. Nevertheless, the functional role of voltage-dependent L-type Ca(2+) channels in controlling SAN [Ca(2+)]i release is largely unexplored. Since Cav1.3 is the predominant L-type Ca(2+) channel isoform in SAN cells, we studied [Ca(2+)]i dynamics in isolated cells and ex vivo SAN preparations explanted from wild-type (WT) and Cav1.3 knockout (KO) mice (Cav1.3(-/-)). We found that Cav1.3 deficiency strongly impaired [Ca(2+)]i dynamics, reducing the frequency of local [Ca(2+)]i release events and preventing their synchronization. This impairment inhibited the generation of Ca(2+) transients and delayed spontaneous activity. We also used action potentials recorded in WT SAN cells as voltage-clamp commands for Cav1.3(-/-) cells. Although these experiments showed abolished Ca(2+) entry through L-type Ca(2+) channels in the diastolic depolarization range of KO SAN cells, their sarcoplasmic reticulum Ca(2+) load remained normal. β-Adrenergic stimulation enhanced pacemaking of both genotypes, thou...Continue Reading

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Citations

Jul 5, 2016·The Journal of Physiology·Pietro MesircaMatteo E Mangoni
May 26, 2018·Cardiovascular Research·Nabil El KhouryCéline Fiset
Dec 5, 2017·Pflügers Archiv : European journal of physiology·Futoshi ToyodaHiroshi Matsuura
Jul 1, 2020·Pflügers Archiv : European journal of physiology·Angelo G TorrenteMatteo E Mangoni
Nov 27, 2018·Cardiovascular Research·Heather Y Small, Tomasz J Guzik
Jul 25, 2019·International Journal of Molecular Sciences·Arturo AndradeLaura Londrigan
Feb 11, 2020·Frontiers in Physiology·Dario DiFrancesco
May 16, 2020·Frontiers in Pharmacology·Zsófia KohajdaNorbert Nagy
Oct 17, 2020·Journal of the American Heart Association·Maria PetkovaHalina Dobrzynski
Oct 10, 2020·The Biochemical Journal·Stephan De WaardMichel Ronjat
Oct 6, 2020·Annual Review of Pharmacology and Toxicology·Pietro MesircaMatteo E Mangoni
Feb 9, 2021·Journal of Molecular and Cellular Cardiology·Bryana M LevitanJonathan Satin
Apr 20, 2021·Frontiers in Genetics·Michael J WallacePeter J Mohler
Jun 16, 2021·Progress in Biophysics and Molecular Biology·Mattia L DiFrancescoMatteo E Mangoni
Jul 24, 2021·Progress in Biophysics and Molecular Biology·Delphine Mika, Rodolphe Fischmeister
Jul 23, 2021·GeroScience·Sabrina ChoiClaudia M Moreno
Aug 27, 2021·Frontiers in Cardiovascular Medicine·Daniel TurnerRajan Sah
Aug 28, 2020·Progress in Biophysics and Molecular Biology·Richard B RobinsonPenelope A Boyden

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