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Science 285 (5435): 1929-1931

Copyright © 1999 by the American Association for the Advancement of Science

Acute Activation of Maxi-K Channels (hSlo) by Estradiol Binding to the beta  Subunit

Miguel A. Valverde, 1* Patricio Rojas, 2 Julio Amigo, 2 Diego Cosmelli, 2 Patricio Orio, 2 Maria I. Bahamonde, 2 Giovanni E. Mann, 4 Cecilia Vergara, 2 Ramon Latorre 23

Maxi-K channels consist of a pore-forming alpha  subunit and a regulatory beta  subunit, which confers the channel with a higher Ca2+ sensitivity. Estradiol bound to the beta  subunit and activated the Maxi-K channel (hSlo) only when both alpha  and beta  subunits were present. This activation was independent of the generation of intracellular signals and could be triggered by estradiol conjugated to a membrane-impenetrable carrier protein. This study documents the direct interaction of a hormone with a voltage-gated channel subunit and provides the molecular mechanism for the modulation of vascular smooth muscle Maxi-K channels by estrogens.

1 Departament de Ciències Experimentals i de la Salut, Universidad Pompeu Fabra, C/Doctor Aiguader 80, 08003 Barcelona, Spain.
2 Departmento de Biología, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile, and Centro de Estudios Cientificos de Santiago, Casilla 16443, Santiago 9, Chile.
3 Department of Anesthesiology, University of California Los Angeles, Los Angeles, CA 90095-1778, USA.
4 Centre for Cardiovascular Biology and Medicine, School of Biomedical Sciences, King's College London, London SE1 9RT, UK.
*   To whom correspondence should be addressed. E-mail: miguel.valverde{at}cexs.upf.es

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O. Baltatu, C. Cayla, R. Iliescu, D. Andreev, C. Jordan, and M. Bader (2002)
J. Am. Soc. Nephrol. 13, 2681-2687
   Abstract »    Full Text »    PDF »
Molecular Basis of Pimarane Compounds as Novel Activators of Large-Conductance Ca2+-Activated K+ Channel alpha -Subunit.
Y. Imaizumi, K. Sakamoto, A. Yamada, A. Hotta, S. Ohya, K. Muraki, M. Uchiyama, and T. Ohwada (2002)
Mol. Pharmacol. 62, 836-846
   Abstract »    Full Text »    PDF »
17beta -Estradiol Benzoate Decreases the AHP Amplitude in CA1 Pyramidal Neurons.
A. Kumar and T. C. Foster (2002)
J Neurophysiol 88, 621-626
   Abstract »    Full Text »    PDF »
New Disguises for an Old Channel: MaxiK Channel {beta}-Subunits.
P. Orio, P. Rojas, G. Ferreira, and R. Latorre (2002)
Physiology 17, 156-161
   Abstract »    Full Text »    PDF »
Bisphenol A Inhibits Cl- Secretion by Inhibition of Basolateral K+ Conductance in Human Airway Epithelial Cells.
Y. Ito, S. Sato, M. Son, M. Kondo, H. Kume, K. Takagi, and K. Yamaki (2002)
J. Pharmacol. Exp. Ther. 302, 80-87
   Abstract »    Full Text »    PDF »
Opposing actions of adrenal androgens and glucocorticoids on alternative splicing of Slo potassium channels in bovine chromaffin cells.
G.-J. Lai and D. P. McCobb (2002)
PNAS 99, 7722-7727
   Abstract »    Full Text »    PDF »
Ethylbromide Tamoxifen, a Membrane-Impermeant Antiestrogen, Activates Smooth Muscle Calcium-Activated Large-Conductance Potassium Channels from the Extracellular Side.
G. M. Dick, A. C. Hunter, and K. M. Sanders (2002)
Mol. Pharmacol. 61, 1105-1113
   Abstract »    Full Text »    PDF »
Vitamin E But Not 17beta -Estradiol Protects against Vascular Toxicity Induced by beta -Amyloid Wild Type and the Dutch Amyloid Variant.
F. J. Munoz, C. Opazo, G. Gil-Gomez, G. Tapia, V. Fernandez, M. A. Valverde, and N. C. Inestrosa (2002)
J. Neurosci. 22, 3081-3089
   Abstract »    Full Text »    PDF »
Phosphorylation-dependent Functional Coupling of hSlo Calcium-dependent Potassium Channel and Its hbeta 4 Subunit.
P. Jin, T. M. Weiger, Y. Wu, and I. B. Levitan (2002)
J. Biol. Chem. 277, 10014-10020
   Abstract »    Full Text »    PDF »
Distribution, Neuronal Colocalization, and 17{beta}-E2 Modulation of Small Conductance Calcium-Activated K+ Channel (SK3) mRNA in the Guinea Pig Brain.
M. A. Bosch, M. J. Kelly, and O. K. Ronnekleiv (2002)
Endocrinology 143, 1097-1107
   Abstract »    Full Text »    PDF »
Natural Bile Acids and Synthetic Analogues Modulate Large Conductance Ca2+-activated K+ (BKCa) Channel Activity in Smooth Muscle Cells.
A. M. Dopico, J. V. Walsh Jr., and J. J. Singer (2002)
J. Gen. Physiol. 119, 251-273
   Abstract »    Full Text »    PDF »
Estrogen replacement therapy, atherosclerosis, and vascular function.
T. S Mikkola and T. B Clarkson (2002)
Cardiovasc Res 53, 605-619
   Abstract »    Full Text »    PDF »

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