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Endostatin inhibits T-type Ca2+ channel current in guinea pig ventricular myocyte

Jumpei Yasuda1, Muneyoshi Okada, Hideyuki Yamawaki

  • 1Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35-1, Towada-shi, Aomori 034-8628, Japan.

The Journal of Veterinary Medical Science
|May 8, 2015
PubMed

Insights

Endostatin, an angiogenesis inhibitor, was found to significantly inhibit T-type calcium channels in cardiac myocytes. This suggests endostatin may play a role in regulating cardiac function and hypertrophy.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Ion Channel Function

Background:

  • Endostatin, derived from collagen XVIII, is an endogenous angiogenesis inhibitor with elevated levels in cardiovascular diseases.
  • Low voltage-activated T-type calcium channels are typically absent in adult ventricular myocytes but their re-expression is linked to cardiac hypertrophy.
  • The role of endostatin in modulating cardiac ion channel activity, specifically T-type calcium channels, remains largely unexplored.

Purpose of the Study:

  • To investigate the direct effects of endostatin on T-type calcium channel currents in adult cardiac myocytes.
  • To determine if endostatin selectively targets T-type calcium channels over L-type calcium channels in the heart.

Main Methods:

  • Utilized the whole-cell patch clamp technique on freshly isolated adult guinea pig ventricular myocytes.
  • These myocytes were chosen for their exceptional expression of T-type calcium channels, allowing for direct electrophysiological assessment.

Main Results:

  • Endostatin at 300 ng/ml demonstrated no significant effect on L-type calcium channel current.
  • Conversely, endostatin significantly inhibited the T-type calcium channel current in the studied cardiac myocytes.

Conclusions:

  • Endostatin acts as a potent endogenous inhibitor of T-type calcium channels within cardiac myocytes.
  • These findings suggest a novel mechanism by which endostatin may influence cardiac electrophysiology and potentially impact the development of cardiac hypertrophy.

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