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Characterization of Ca(2+) channels involved in endothelin-1-induced mitogenic responses in vascular smooth muscle

Y Kawanabe1, Y Okamoto, N Hashimoto

  • 1Department of Neurosurgery, Faculty of Medicine, Kyoto University, Kyoto, Japan. kawanabe@kuhp.kyoto-u.ac.jp

European Journal of Pharmacology
|June 30, 2001
PubMed

Insights

Endothelin-1 triggers cell growth by increasing intracellular calcium. Voltage-independent calcium channels, not L-type channels, are key. These include nonselective cation channels and store-operated channels.

Area of Science:

  • Pharmacology
  • Cell Biology
  • Cardiovascular Research

Background:

  • Endothelin-1 is a potent vasoconstrictor and mitogen.
  • Calcium influx is critical for smooth muscle cell proliferation.
  • The specific calcium channels mediating endothelin-1's mitogenic effects require elucidation.

Purpose of the Study:

  • To characterize the calcium channels involved in endothelin-1-induced mitogenesis in rat aortic smooth muscle cells (A7r5).
  • To determine the relative contributions of different calcium channel types to the mitogenic response.

Main Methods:

  • A7r5 cells were stimulated with endothelin-1.
  • Intracellular calcium concentrations were measured.
  • The effects of calcium channel blockers, including nifedipine, LOE 908, and SK&F 96365, were assessed.
  • The roles of voltage-operated calcium channels (VOCCs) and voltage-independent calcium channels (VICCs) were investigated.

Main Results:

  • Endothelin-1 induced a biphasic increase in intracellular calcium and a mitogenic response.
  • L-type VOCCs play a minor role in this response.
  • Voltage-independent calcium channels (VICCs) are crucial for endothelin-1-induced mitogenesis.
  • VICCs comprise nonselective cation channels (NSCC-1, NSCC-2) and store-operated calcium channels (SOCCs).
  • NSCC-1, NSCC-2, and SOCCs contributed 35%, 30%, and 35% respectively to the nifedipine-resistant calcium influx.

Conclusions:

  • Voltage-independent calcium channels, specifically NSCC-1, NSCC-2, and SOCCs, are the primary mediators of endothelin-1-induced mitogenesis in A7r5 cells.
  • Targeting these channels could offer therapeutic strategies for conditions involving vascular smooth muscle proliferation.

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