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Ras reduces L-type calcium channel current in cardiac myocytes. Corrective effects of L-channels and SERCA2 on

P D Ho1, J S Fan, N L Hayes

  • 1SDSU Heart Institute and Department of Biology, San Diego State University, San Diego, California, USA.

Circulation Research
|January 5, 2001
PubMed

Insights

Ras activation in heart cells disrupts calcium handling and reduces muscle function. Restoring L-channel expression may correct these heart failure-related defects.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cellular Physiology

Background:

  • Heart failure involves disrupted intracellular calcium ([Ca(2+)](i)) regulation.
  • Ras signaling pathways are implicated in cardiac dysfunction.

Purpose of the Study:

  • To investigate the impact of Ras activation on cardiac myocyte calcium handling and function.
  • To determine the role of L-channels in Ras-mediated cardiac effects.

Main Methods:

  • Constitutively active Ras (Ha-Ras(V12)) was expressed in cardiac myocytes.
  • Intracellular calcium ([Ca(2+)](i)) was monitored using fluorescence and electrophysiology.
  • L-channel expression and activity were assessed.

Main Results:

  • Ha-Ras(V12) reduced contractile calcium transients and L-channel currents.
  • Calcium loading of the sarcoplasmic reticulum increased, indicating impaired excitation-calcium release coupling.
  • Coexpression of L-channels and SERCA2 ameliorated Ras-induced calcium dysregulation and myofibril reduction.

Conclusions:

  • Ras activation downregulates L-channel expression in cardiac myocytes.
  • This L-channel downregulation contributes to the pathophysiology of heart failure.
  • Targeting L-channel expression may offer a therapeutic strategy for Ras-related cardiac diseases.

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