Ras reduces L-type calcium channel current in cardiac myocytes: Corrective effects of L-channels and SERCA2 on [Ca2+]i regulation and cell morphology

Peter D. Ho, Jing Song Fan, Nicole L. Hayes, Nehad Saada, Philip T. Palade, Christopher C. Glembotski, Patrick M. McDonough

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Heart failure is associated with dysregulation of intracellular calcium ([Ca2+]i), reduction in myofibrils, and increased activation of Ras, a regulator of signal-transduction pathways. To evaluate the potential effects of Ras on [Ca2+]i, we expressed constitutively active Ras (Ha-RasV12) in cardiac myocytes and monitored [Ca2+]i via fluorescence and electrophysiological techniques. Ha-RasV12 reduced the magnitude of the contractile calcium transients. Unexpectedly, however, calcium loading of the sarcoplasmic reticulum was increased, suggesting that Ha-RasV12 introduces a defect in excitation-calcium release coupling. Consistent with this idea, L-channel calcium currents were reduced by Ha-RasV12, which also downregulated the activity of the L-channel gene promoter. Coexpression of L-channels and SERCA2 largely corrected Ha-RasV12-induced dysregulation of [Ca2+]i. Furthermore, whereas Ha-RasV12 downregulated myofibrils, this effect was blocked by coexpression of L-channels. These results suggest that Ras downregulates L-channel expression, which may play a pathophysiological role in cardiac disease.

Original languageEnglish (US)
Pages (from-to)63-69
Number of pages7
JournalCirculation research
Volume88
Issue number1
DOIs
StatePublished - Jan 19 2001
Externally publishedYes

Keywords

  • Cardiac hypertrophy
  • L-type calcium channel
  • Ras
  • SERCA2

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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