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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

Src family tyrosine kinases inhibit single L-type: Ca2+ channel activity in human atrial myocytes

Frank Schröder1, Gunnar Klein, Tanja Frank

  • 1Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Strasse 1, Hannover 30625, Germany. schroeder.f@mh-hannover.de

Journal of Molecular and Cellular Cardiology
|September 8, 2004
PubMed
Abstract

Insights

Tyrosine kinases (TKs) regulate L-type Ca(2+) channel activity in human atrial cells. Src family TKs inhibit LTCCs through protein kinase C, independent of PKA and phosphatases.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cell Physiology

Background:

  • Tyrosine kinases (TKs) are known regulators of L-type Ca(2+) channels (LTCCs).
  • LTCC gating properties are altered in human atrial myocytes during disease states.
  • The specific role of TKs in human atrial myocyte LTCC activity remains uncharacterized.

Purpose of the Study:

  • To investigate the role of tyrosine kinases in regulating single LTCC activity in human atrial myocytes.
  • To elucidate the molecular pathways involved in TK-mediated LTCC modulation.

Main Methods:

  • Single LTCC activity was recorded in isolated human atrial myocytes.
  • Pharmacological inhibitors of TKs (genistein, PP1) and phosphatases were used.
  • Modulation of protein kinase A (PKA) and protein kinase C (PKC) pathways was assessed.

Main Results:

  • TK inhibition (genistein, PP1) enhanced LTCC current, availability, and open probability.
  • Tyrosine phosphatase inhibition reduced LTCC activity, indicating reciprocal regulation.
  • TK effects were independent of PKA and serine/threonine phosphatases but required PKC.

Conclusions:

  • Src family TKs inhibit LTCC activity in human atrial myocytes.
  • This inhibition occurs via a PKC-dependent pathway.
  • The pathway is independent of PKA and serine/threonine phosphatases types I and IIa.

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