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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 and Keith A. Hruska
Proceedings of the National Academy of Sciences of the United States of America
Vol. 93, No. 5 (Mar. 5, 1996), pp. 1864-1869
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/38429
Page Count: 6
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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 (Gm) 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 α 1-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 Gm in response to hypotonic swelling following CMS. Antisense ODNs to α 1S, and α 1D, sense ODNs to 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 be determined from our data. Our data indicate that the α 1C gene product is involved in the Gm 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.
Proceedings of the National Academy of Sciences of the United States of America © 1996 National Academy of Sciences