Cell Biochemistry and Biophysics

, Volume 31, Issue 1, pp 65–79 | Cite as

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


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.

Index Entries

Osteoblast osteosarcoma UMR-106.01 calcium channels swelling regulatory volume decrease (RVD) dihydropyridine (DHP) hypotonic Fura-2 


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Copyright information

© Humana Press, Inc 1999

Authors and Affiliations

  • Neil Kizer
    • 1
  • Laura Harter
    • 1
  • Keith Hruska
    • 1
  • Ulises Alvarez
    • 1
  • Randall Duncan
    • 2
  1. 1.Renal DivisionBarnes-Jewish Hospital at the Washington University Medical CenterSt. Louis
  2. 2.Department of Orthopedic SurgeryIndiana University School of MedicineIndianapolis

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