Mechanism of down-regulation of L-type Ca2+ channel in the proliferating smooth muscle cells of rat aorta

Eikichi Ihara, Katsuya Hirano, Mayumi Hirano, Junji Nishimura, Hajime Nawata, Hideo Kanaide

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Abstract

The mechanism of down-regulation of L-type Ca2+ channel (L-VOC) was investigated in rat aortic smooth muscle cells in primary culture. On culture days 3-5, the cells actively incorporated the 5-bromo-2′-deoxy-uridine (BrdU), and did not respond to K+ depolarization nor express α1C subunit of L-VOC. At confluence on day 8, BrdU incorporation decreased, and the cells up-regulated α1C subunit mRNA, expressed α1C subunit protein at cell periphery, and responded to K+ depolarization. Treating the proliferating cells on day 3 with serum-free media or 10 μM PD98059, a MAP kinase kinase inhibitor, for 2 days induced the expression of α1C subunit protein and the responsiveness to K+ depolarization. However, the serum starvation, but not PD98059, decreased the BrdU incorporation and increased the α1C subunit mRNA. It is concluded that the expression of L-VOC is substantially suppressed in the proliferating cells due to two mechanisms; a MAP kinase-mediated post-transcriptional down-regulation and the transcriptional down-regulation by additional mitogenic signals.

Original languageEnglish
Pages (from-to)242-251
Number of pages10
JournalJournal of Cellular Biochemistry
Volume87
Issue number2
DOIs
Publication statusPublished - Oct 16 2002

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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