| First Author | Louradour J | Year | 2022 |
| Journal | Cells | Volume | 11 |
| Issue | 7 | PubMed ID | 35406677 |
| Mgi Jnum | J:334672 | Mgi Id | MGI:7261638 |
| Doi | 10.3390/cells11071114 | Citation | Louradour J, et al. (2022) L-Type Cav1.3 Calcium Channels Are Required for Beta-Adrenergic Triggered Automaticity in Dormant Mouse Sinoatrial Pacemaker Cells. Cells 11(7) |
| abstractText | BACKGROUND: Sinoatrial node cells (SANC) automaticity is generated by functional association between the activity of plasmalemmal ion channels and local diastolic intracellular Ca(2+) release (LCR) from ryanodine receptors. Strikingly, most isolated SANC exhibit a "dormant" state, whereas only a fraction shows regular firing as observed in intact SAN. Recent studies showed that beta-adrenergic stimulation can initiate spontaneous firing in dormant SANC, though this mechanism is not entirely understood. METHODS: To investigate the role of L-type Cav1.3 Ca(2+) channels in the adrenergic regulation of automaticity in dormant SANC, we used a knock-in mouse strain in which the sensitivity of L-type Cav1.2 alpha1 subunits to dihydropyridines (DHPs) was inactivated (Cav1.2(DHP-/-)), enabling the selective pharmacological inhibition of Cav1.3 by DHPs. RESULTS: In dormant SANC, beta-adrenergic stimulation with isoproterenol (ISO) induced spontaneous action potentials (AP) and Ca(2+) transients, which were completely arrested with concomitant perfusion of the DHP nifedipine. In spontaneously firing SANC at baseline, Cav1.3 inhibition completely reversed the effect of beta-adrenergic stimulation on AP and the frequency of Ca(2+) transients. Confocal calcium imaging of SANC showed that the beta-adrenergic-induced synchronization of LCRs is regulated by the activity of Cav1.3 channels. CONCLUSIONS: Our study shows a novel role of Cav1.3 channels in initiating and maintaining automaticity in dormant SANC upon beta-adrenergic stimulation. |
