Authors: K A Smitherman H Sontheimer
Publish Date: 2014/02/01
Volume: 181, Issue: 2, Pages: 125-135
Abstract
Tamoxifen tmx is a nonsteroidal triphenylethylene derivative that is predominantly known as a competitive antagonist at the estrogen receptor and is used in the treatment of breast cancer Recent studies suggest that tamoxifen is also beneficial in the treatment of brain metastases and primary brain tumors Tmx accumulates in brain and its concentration can be up to 46fold higher than in serum Therefore astrocytes may be exposed to tmx in vivoWe use the wholecell patchclamp technique to examine the effects of tmx on voltagedependent cation currents in rat cortical cultures Using biophysical and pharmacological methods we isolate sustained and transient outward potassium currents I KS and I KT respectively inwardly rectifying potassium currents I KIR and transient inward sodium currents I Na We show that that TTXsensitive I Na is completely inhibited by 10 μm tmx within 5 min Similarly tmx blocks I KS but does not inhibit I KT or I KIR at these concentrations Tmx effects are irreversible with 10 min washInterestingly the currents sensitive to tmx are important in growth control of glial cells MacFarlane Sontheimer 1997 Therefore we examine cytotoxic and proliferative effects of tmx Tmx 10 μm is not cytotoxic as judged by trypan blue exclusion However incubation with tmx significantly reduces cell proliferation as examined by 3Hthymidine uptake
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