Low voltage-activated channels in rat pulmonary vein cardiomyocytes: coexistence of a non-selective cationic channel and of T-type Ca channels

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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Acknowledgments

The author is indebted to Dr Ian Findlay for helpful discussions and critical comments on the manuscript.

Funding

This work was financially supported by the University of Tours and the Centre National de la Recherche Scientifique.

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Correspondence to Claire O. Malécot.

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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 (2020). https://doi.org/10.1007/s00424-020-02413-1

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Keywords

  • Calcium channels
  • Non-specific cationic channel
  • LVA currents

Subject codes

  • Basic science research
  • Ion channels/membrane transport
  • Electrophysiology