Inhibition of a cardiac sarcoplasmic reticulum chloride channel by tamoxifen.
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.
Beca
Sanja
S
Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
Pavlov
Evgeny
E
Kargacin
Margaret E
ME
Aschar-Sobbi
Roozbeh
R
French
Robert J
RJ
Kargacin
Gary J
GJ
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*
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