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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}

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Mol. Pharmacol. 61, 1105-1113
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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 »
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 »
Endothelium-independent effect of estrogen on Ca2+-activated K+ channels in human coronary artery smooth muscle cells.
R. E White, G. Han, M. Maunz, C. Dimitropoulou, A. M El-Mowafy, R. S Barlow, J. D Catravas, C. Snead, G. O Carrier, S. Zhu, et al. (2002)
Cardiovasc Res 53, 650-661
   Abstract »    Full Text »    PDF »
Presynaptic Ca2+-Activated K+ Channels in Glutamatergic Hippocampal Terminals and Their Role in Spike Repolarization and Regulation of Transmitter Release.
H. Hu, L.-R. Shao, S. Chavoshy, N. Gu, M. Trieb, R. Behrens, P. Laake, O. Pongs, H. G. Knaus, O. P. Ottersen, et al. (2001)
J. Neurosci. 21, 9585-9597
   Abstract »    Full Text »    PDF »
The Estrogen Trinity: Membrane, Cytosolic, and Nuclear Effects.
A. Nadal, M. Diaz, and M. A. Valverde (2001)
Physiology 16, 251-255
   Abstract »    Full Text »    PDF »
Okadaic acid-sensitive activation of Maxi Cl- channels by triphenylethylene antioestrogens in C1300 mouse neuroblastoma cells.
M. Diaz, M. I Bahamonde, H. Lock, F. J Munoz, S. P Hardy, F. Posas, and M. A Valverde (2001)
J. Physiol. 536, 79-88
   Abstract »    Full Text »    PDF »
The C Terminus of the Human Nicotinic {alpha}4{beta}2 Receptor Forms a Binding Site Required for Potentiation by an Estrogenic Steroid.
K. Paradiso, J. Zhang, and J. H. Steinbach (2001)
J. Neurosci. 21, 6561-6568
   Abstract »    Full Text »    PDF »
Role of estrogen in modulating EDHF-mediated dilations in the female rat middle cerebral artery.
E. M. Golding and T. E. Kepler (2001)
Am J Physiol Heart Circ Physiol 280, H2417-H2423
   Abstract »    Full Text »    PDF »

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