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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
10:53

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents

Published on: July 3, 2013

cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes

M Rivet-Bastide1, G Vandecasteele, S Hatem

  • 1Laboratoire de Cardiologie Cellulaire et Moléculaire, Institut National de la Santé et de la Recherche Médicale U-446, Université de Paris-Sud, Faculté de Pharmacie, F-92296 Châtenay-Malabry, France.

The Journal of Clinical Investigation
|June 1, 1997
PubMed

Insights

Erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA) enhances cardiac L-type Ca2+ current in human atrial cells by inhibiting phosphodiesterase 2 (PDE2). This suggests PDE2 regulates basal Ca2+ influx in these cells.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Pharmacology
  • Cell Signaling

Background:

  • Erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA) is a known inhibitor of adenosine deaminase.
  • Recent studies identified EHNA as an inhibitor of phosphodiesterase 2 (PDE2) with a Ki of approximately 1 microM.
  • EHNA showed negligible effects on other PDE isozymes like PDE1, PDE3, and PDE4.

Purpose of the Study:

  • To investigate the role of PDE2 in regulating cardiac L-type Ca2+ current (ICa) in human atrial myocytes.
  • To determine if EHNA's effect on ICa is mediated by PDE2 inhibition.

Main Methods:

  • Freshly isolated human atrial myocytes were used to examine the effect of EHNA on ICa.
  • Electrophysiological recordings were performed to measure changes in ICa amplitude and kinetics.
  • Experiments included varying EHNA concentrations, using other PDE inhibitors, and manipulating intracellular cyclic nucleotide levels.

Main Results:

  • EHNA (0.1-10 microM) significantly increased basal ICa amplitude in human atrial myocytes by approximately 80% at 1 microM.
  • EHNA did not alter current-voltage or inactivation curves, and its effect was not additive with isoprenaline.
  • The effect was specific to PDE2 inhibition, as other adenosine deaminase inhibitors or adenosine did not affect ICa, and EHNA was ineffective in rat myocytes.

Conclusions:

  • Basal cardiac L-type Ca2+ current in human atrial myocytes is regulated by PDE2 activity.
  • PDE2 inhibition by EHNA leads to increased ICa, suggesting a role in controlling intracellular cyclic nucleotide levels.
  • Both PDE2 and PDE3 may contribute to maintaining low cyclic nucleotide concentrations in the absence of cyclase stimulation.

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