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Updated: Aug 15, 2026

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

Calmodulin antagonist W7 directly inhibits f-type current in rabbit sino-atrial cells

Aurélien Chatelier1, Barbara Renaudon, Jocelyn Bescond

  • 1Institut de Physiologie et Biologie Cellulaires, CNRS UMR 6187, Université de Poitiers, 86022 Poitiers Cedex, France.

European Journal of Pharmacology
|September 29, 2005
PubMed

Insights

Calcium-calmodulin does not directly modulate pacemaker (I(f)) channels. However, the calmodulin antagonist W7 alters I(f) channel voltage-dependent properties, suggesting new bradycardic drug development pathways.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Neuroscience

Background:

  • Pacemaker (I(f)) channels are crucial for heart rhythm.
  • Cyclic nucleotide-gated channels are modulated by Ca2+-calmodulin.
  • The role of Ca2+-calmodulin in I(f) channel function is not fully understood.

Purpose of the Study:

  • To investigate the effect of Ca2+-calmodulin and W7 on the apparent affinity of pacemaker (I(f)) channels for cAMP.
  • To determine if Ca2+-calmodulin directly modulates I(f) channel activity.

Main Methods:

  • Patch-clamp technique in inside-out macro-patch configuration.
  • Rabbit sino-atrial cells were used.
  • Effects of intracellular calmodulin perfusion and W7 on I(f) channel activity and cAMP-induced shifts were analyzed.

Main Results:

  • Intracellular calmodulin perfusion did not affect f-channel activity or cAMP-induced shifts.
  • W7 decreased maximal conductance and shifted the current activation curve towards negative potentials.
  • W7's effects were independent of cAMP binding and did not prevent cAMP-induced shifts.

Conclusions:

  • Pacemaker (I(f)) channels are not directly modulated by Ca2+-calmodulin, unlike cyclic nucleotide-gated channels.
  • W7 alters the voltage-dependent properties of I(f) channels independently of cAMP binding.
  • These findings suggest W7 as a potential lead for developing novel bradycardic drugs.

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