Volume regulatory decrease in UMR-106.01 cells is mediated by specific α1 subunits of L-type calcium channels

Neil Kizer, Laura Harter, Keith Hruska, Ulises Alvarez, Randall Duncan

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

An early cellular response of osteoblasts to swelling is plasma membrane depolarization, accompanied by a transient increase in intracellular calcium ([Ca2+]i), which initiates regulatory volume decrease (RVD). The authors have previously demonstrated a hypotonically induced depolarization of the osteoblast plasma membrane, sufficient to open L-type Ca channels and mediate Ca2+ influx. Herein is described the initiation of RVD in UMR-106.01 cells, mediated by hypotonically induced [Ca2+]i transients resulting from the activation of specific isoforms of L-type Ca channels. The authors further demonstrate that substrate interaction determines which specific α1 Ca channel subunit isoform predominates and mediates Ca2+ entry and RVD. Swelling-induced [Ca2+]i transients, and RVD in cells grown on a type I collagen matrix, are inhibited by removal of Ca from extracellular solutions, dihydropyridines, and antisense oligodeoxynucleotides directed exclusively to the α1C isoform of the L-type Ca channel. Ca2+ transients and RVD in cells grown on untreated glass cover slips were inhibited by similar maneuvers, but only by antisense oligodeoxynucleotides directed to the α1S isoform of the L-type Ca channel. This represents the first molecular identification of the Ca channels that transduce the initiation signal for RVD by osteoblastic cells.

Original languageEnglish
Pages (from-to)65-79
Number of pages15
JournalCell Biochemistry and Biophysics
Volume31
Issue number1
DOIs
StatePublished - 1999

Keywords

  • Calcium channels
  • Dihydropyridine (DHP)
  • Fura-2
  • Hypotonic
  • Osteoblast
  • Osteosarcoma
  • Regulatory volume decrease (RVD)
  • Swelling
  • UMR-106.01

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