HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 23, 21739-21747, June 10, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/23/21739    most recent M413953200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pérez, G. J. Search for Related Content PubMed PubMed Citation Articles by Pérez, G. J. Social Bookmarking                      What's this?

Dual Effect of Tamoxifen on Arterial KCa Channels Does Not Depend on the Presence of the 1 Subunit^*

Guillermo J. Pérez

From the Masonic Medical Research Laboratory, Utica, New York 13501

Tamoxifen has been reported to directly activate large conductance calcium-activated potassium (KCa) channels through the KCa 1 subunit, suggesting a cardio-protective role of this compound. The present study using knock-out (KO) mice for the KCa channel 1 subunit was aimed at understanding the molecular mechanisms of the effects of tamoxifen on arterial smooth muscle KCa channels. Single channel studies were conducted in excised patches from cerebral artery myocytes from both wild-type and KO animals. The present data demonstrated that tamoxifen can inhibit arterial KCa channels due to a major decrease in channel open probability (P_o), a mechanism different from the reduction in single channel amplitude reported previously and also observed in the present work. A tamoxifen-induced decrease in P_o was present in arterial KCa channels from both wild-type and 1 KO animals. This inhibition was concentration-dependent and partially reversible with a half-maximal concentration constant IC₅₀ of 2.6 µM. The effect of tamoxifen was actually dual Single channel kinetic analysis showed that tamoxifen shortens both mean closed time and mean open time; the latter is probably due to an intermediate duration voltage-independent blocking mechanism. Thus, tamoxifen block would predominate when KCa channel P_o is >0.1–0.2, limiting the maximum P_o, whereas a leftward shift in voltage or Ca²⁺ activation curves can be observed for P_o values lower than those values. This dual effect of tamoxifen appears to be independent of the 1 subunit. The molecular specificity of tamoxifen, or eventually other xenoestrogen derivatives, for the KCa channel 1 subunit is uncertain.

Received for publication, December 13, 2004 , and in revised form, April 8, 2005.

^* This work was supported by Grant K01 HL073161-03 from the National Institutes of Health and Grant 0130570T from the American Heart Association, New York affiliate. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker St., Utica, NY 13501. Tel.: 315-735-2217 (ext. 155); Fax: 315-735-5648; E-mail: gperez{at}mmrl.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Tong and R. K. Duncan Tamoxifen inhibits BK channels in chick cochlea without alterations in voltage-dependent activation Am J Physiol Cell Physiol, July 1, 2009; 297(1): C75 - C85. [Abstract] [Full Text] [PDF]

				X.-H. Sun, J.-P. Ding, H. Li, N. Pan, L. Gan, X.-L. Yang, and H.-B. Xu Activation of Large-Conductance Calcium-Activated Potassium Channels by Puerarin: The Underlying Mechanism of Puerarin-Mediated Vasodilation J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 391 - 397. [Abstract] [Full Text] [PDF]

				A. N. Bukiya, J. Liu, L. Toro, and A. M. Dopico beta1 (KCNMB1) Subunits Mediate Lithocholate Activation of Large-Conductance Ca2+-Activated K+ Channels and Dilation in Small, Resistance-Size Arteries Mol. Pharmacol., August 1, 2007; 72(2): 359 - 369. [Abstract] [Full Text] [PDF]

				G. Coiret, A.-S. Borowiec, P. Mariot, H. Ouadid-Ahidouch, and F. Matifat The Antiestrogen Tamoxifen Activates BK Channels and Stimulates Proliferation of MCF-7 Breast Cancer Cells Mol. Pharmacol., March 1, 2007; 71(3): 843 - 851. [Abstract] [Full Text] [PDF]

				D. N. Krause, S. P. Duckles, and D. A. Pelligrino Influence of sex steroid hormones on cerebrovascular function J Appl Physiol, October 1, 2006; 101(4): 1252 - 1261. [Abstract] [Full Text] [PDF]