Abstract
In rat pulmonary vein (PV) cardiomyocytes (CM), norepinephrine (NE) induces an automatic activity consisting of bursts of slow action potentials which depend on Ca2+ (upstroke) and Na+ (inter-burst) channels. Our objective was to characterize low voltage-activated (LVA) currents in rat PVCM susceptible to trigger this activity. Whole-cell ICa (5 mM Ca2+) was recorded from − 100 mV with classical Na+- and K+-free solutions. A fast LVA ICa (FLVA-ICa), present in ≈ 56% of PVCM between ~ − 50 to − 20 mV, was blocked by 10 μM TTX and markedly increased by addition of NaCl (1 or 3 mM) or KCl (5 or 10 mM). Permeability ratios P′Ca/PNa and P′Ca/PK calculated for bi-ionic conditions were respectively 2.25 ± 0.51 and 1.88 ± 0.25, and not different from a value of 2. FLVA-ICa was increased by 10 μM NE and 300 nM BayK8644, decreased by 5 μM nifedipine but not blocked by ranolazine (10 μM). NiCl2 (40 μM) and TTA-A2 (10 or 100 nM) increased FLVA-ICa. Similar results were obtained in left atrial (LA) CM. Neither Ba2+ nor Sr2+ alone could permeate the FLVA channel or block Ca2+ influx but revealed a large slower activating and inactivating LVA Ca2+ current (SLVA-ICa), present in 10 out of 80 PVCM, absent in LACM, and partially inhibited by 100 nM TTA-A2. Therefore, the ionic channel underlying FLVA-ICa is likely a fast voltage-gated non-selective channel with a dihydropyridine binding site. SLVA-ICa might correspond to Ca2+ influx through Cav3.x channels and contribute to triggering NE-induced automatic activity in the PV myocardial sleeve.
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Abbreviations
- CM:
-
Cardiomyocytes
- FLVA:
-
Fast low voltage-activated
- FSLVA:
-
Fast activating and slow inactivating low voltage-activated
- ICa :
-
Calcium current
- INa :
-
Sodium current
- LA:
-
Left atria
- LVA:
-
Low voltage-activated
- NE:
-
Norepinephrine
- PV:
-
Pulmonary vein
- SLVA:
-
Slow low voltage-activated
- TTX:
-
Tetrodotoxin
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The author is indebted to Dr Ian Findlay for helpful discussions and critical comments on the manuscript.
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This work was financially supported by the University of Tours and the Centre National de la Recherche Scientifique.
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Malécot, C.O. Low voltage-activated channels in rat pulmonary vein cardiomyocytes: coexistence of a non-selective cationic channel and of T-type Ca channels. Pflugers Arch - Eur J Physiol 472, 1019–1029 (2020). https://doi.org/10.1007/s00424-020-02413-1
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DOI: https://doi.org/10.1007/s00424-020-02413-1