title: Inhibition of a cardiac sarcoplasmic reticulum chloride channel by tamoxifen.
abstract: Anion and cation channels present in the sarcoplasmic reticulum (SR) are believed to be necessary to maintain the electroneutrality of SR membrane during Ca(2+) uptake by the SR Ca(2+) pump (SERCA). Here we incorporated canine cardiac SR ion channels into lipid bilayers and studied the effects of tamoxifen and other antiestrogens on these channels. A Cl(-) channel was identified exhibiting multiple subconductance levels which could be divided into two primary conductance bands. Tamoxifen decreases the time the channel spends in its higher, voltage-sensitive band and the mean channel current. The lower, voltage-insensitive, conductance band is not affected by tamoxifen, nor is a K(+) channel present in the cardiac SR preparation. By examining SR Ca(2+) uptake, SERCA ATPase activity, and SR ion channels in the same preparation, we also estimated SERCA transport current, SR Cl(-) and K(+) currents, and the density of SERCA, Cl(-), and K(+) channels in cardiac SR membranes.
authors.affiliation: Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Sanja
authors.initials: S
authors.lastname: Beca
authors.forename: Evgeny
authors.initials: E
authors.lastname: Pavlov
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Kargacin
authors.forename: Roozbeh
authors.initials: R
authors.lastname: Aschar-Sobbi
authors.forename: Robert J
authors.initials: RJ
authors.lastname: French
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Kargacin
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D002996:Clomiphene / Q000494:pharmacology; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004594:Electrophysiology; D008051:Lipid Bilayers; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018118:Chloride Channels; D008051:Lipid Bilayers; D015221:Potassium Channels; D013629:Tamoxifen; D002996:Clomiphene; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium