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Updated: Jul 2, 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

Novel mechanism for suppression of hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by

Jianying Huang1, Aijie Huang, Qi Zhang

  • 1Center for Interdisciplinary Research in Cardiovascular Sciences, Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia 26506, USA.

The Journal of Biological Chemistry
|September 5, 2008
PubMed

Insights

Receptor-like protein-tyrosine phosphatase-alpha (RPTPα) decreases hyperpolarization-activated cyclic nucleotide-gated (HCN) channel expression and function through tyrosine dephosphorylation, impacting cardiac and neuronal activity.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Cardiology

Background:

  • Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are modulated by tyrosine phosphorylation.
  • Previous work highlighted the role of Src in increasing HCN channel activity.

Purpose of the Study:

  • To investigate a novel mechanism of decreased tyrosine phosphorylation on HCN channel properties.
  • To elucidate the role of receptor-like protein-tyrosine phosphatase-alpha (RPTPα) in regulating HCN channel function.

Main Methods:

  • HEK293 cell expression studies.
  • Biochemical assays for protein expression and phosphorylation.
  • Confocal imaging for channel localization.
  • Pharmacological inhibition of tyrosine phosphatase activity in cardiac tissue.

Main Results:

  • RPTPα significantly inhibited HCN2 channel expression and surface localization in HEK293 cells.
  • RPTPα decreased tyrosine phosphorylation of the HCN2 channel protein.
  • RPTPα was detected in cardiac ventricles with altered expression during development.
  • Inhibition of RPTPα activity shifted HCN channel-generated currents (I(f)) to physiological voltages with faster kinetics.

Conclusions:

  • RPTPα plays a critical role in regulating HCN channel function through tyrosine dephosphorylation.
  • These findings are relevant to cardiac physiology and neuronal function, where both HCN channels and RPTPα are expressed.

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