Co-existence of a fast tetrodotoxin-sensitive low voltage-activated non selective Na/Ca/K channel and of T-type Ca channels in rat isolated pulmonary vein cardiomyocytes - 25/09/20
Résumé |
Introduction |
Ectopic foci in pulmonary veins (PV) are involved in the onset of atrial fibrillation. Norepinephrine (NE) induces an automatic activity occurring in bursts in rat PV cardiomyocytes (CM) which depends on Ca (upstroke) and Na (inter-burst) channels.
Objective |
To characterize low voltage-activated (LVA) Ca currents in rat PVCM susceptible to trigger ectopic foci.
Method |
Whole-cell ICa (5mM Ca) was recorded from -100mV with classical Na- and K-free solutions at room temperature in enzymatically isolated PVCM from male Wistar rats.
Results |
A fast LVA ICa (FLVA-ICa; −1.5±0.2 pA/pF, n=45; 26% of peak ICa, max recorded at +20mV) was activated between −55 and −20mV in ∼56% of PVCM and blocked by 10μM tetrodotoxin (TTX). In that, it was similar to the reported TTX-sensitive Ca current. However, it was markedly increased by addition of NaCl (1 or 3mM) or KCl (5 or 10mM). Permeability ratios P’Ca/PNa and P’Ca/PK calculated for bi-ionic conditions were respectively 2.25±0.51 (n=6) and 1.88±0.25 (n=14), and not different from a value of 2. NE (10μM, n=13) increased FLVA-ICa and negatively shifted its activation threshold, an effect partially reversed by 5μM Atenolol. It was partially blocked by 5μM Nifedipine (n=5) and increased by 300nM BayK8644 (n=6), but not blocked by Ranolazine (10μM, n=6). NiCl2 (40μM, n=9) and TTA-A2 (10 or 100nM, n=11) increased FLVA-ICa. Neither Ba nor Sr alone could permeate the FLVA channel or block Ca influx but revealed a large slower activating and inactivating LVA Ca current (SLVA-ICa), present in 10 out of 80 PVCM and absent in LACM. SLVA-ICa was partially blocked by 100nM TTA-A2.
Conclusions |
The ionic channel underlying FLVA-ICa is likely a fast voltage-gated non-selective channel permeable to Na/Ca/K with a dihydropyridine binding site. SLVA-ICa might correspond to Ca influx through Cav3.1 channels. The respective role of these channels to triggering ectopic foci in the PV myocardial sleeve remained to be determined.
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Vol 12 - N° 2-4
P. 259 - octobre 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.