Antisense oligodeoxynucleotide inhibition of a swelling-activated cation channel in osteoblast-like osteosarcoma cells

Randall L. Duncan, Neil Kizer, Elizabeth L.R. Barry, Peter A. Friedman, Keith A. Hruska

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

By patch-clamp analysis, we have shown that chronic, intermittent mechanical strain (CMS) increases the activity of stretch-activated cation channels of osteoblast-like UMR-106.01 cells. CMS also produces a swelling- activated whole-cell conductance (G(m)) regulated by varying strain levels. We questioned whether the swelling-activated conductance was produced by stretch-activated cation channel activity. We have identified a gene involved in the increase in conductance by using antisense oligodeoxynucleotides (ODN) derived from the α1-subunit genes of calcium channels found in UMR-106.01 cells (α(1S), α(1C), and α(1D)). We demonstrate that α(1C) antisense ODNs abolish the increase in G(m) in response to hypotonic swelling following CMS. Antisense ODNs to α(1S), and α(1D), sense ODNs in α(1C), and sham permeabilization had no effect on the conductance increase. In addition, during cell-attached patch-clamp studies, antisense ODNs to α(1C) completely blocked the swelling-activated and stretch-activated nonselective cation channel response to strain. Antisense ODNs to α(1S) treatment produced no effect on either swelling-activated or stretch-activated cation channel activity. There were differences in the stretch-activated and swelling- activated cation channel activity, but whether they represent different channels could not he determined from our data. Our data indicate that the α(1C) gene product is involved in the G(m) and the activation of the swelling-activated cation channels induced by CMS. The possibility that swelling-activated cation channel genes are members of the calcium channel superfamily exists, but if α(1C) is not the swelling-activated cation channel itself, then its expression is required for induction of swelling- activated cation channel activity by CMS.

Original languageEnglish
Pages (from-to)1864-1869
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number5
DOIs
StatePublished - Mar 5 1996

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