Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Invitrogen

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 27 October 2006:
Vol. 314. no. 5799, pp. 615 - 620
DOI: 10.1126/science.1132915
Prev | Table of Contents | Next

Research Articles

BKCa-Cav Channel Complexes Mediate Rapid and Localized Ca2+-Activated K+ Signaling

Henrike Berkefeld,1* Claudia A. Sailer,1,3* Wolfgang Bildl,1,2 Volker Rohde,2 Jörg-Oliver Thumfart,1 Silke Eble,1 Norbert Klugbauer,4 Ellen Reisinger,1 Josef Bischofberger,1 Dominik Oliver,1 Hans-Günther Knaus,3 Uwe Schulte,2{dagger} Bernd Fakler1{dagger}

Large-conductance calcium- and voltage-activated potassium channels (BKCa) are dually activated by membrane depolarization and elevation of cytosolic calcium ions (Ca2+). Under normal cellular conditions, BKCa channel activation requires Ca2+ concentrations that typically occur in close proximity to Ca2+ sources. We show that BKCa channels affinity-purified from rat brain are assembled into macromolecular complexes with the voltage-gated calcium channels Cav1.2 (L-type), Cav2.1 (P/Q-type), and Cav2.2 (N-type). Heterologously expressed BKCa-Cav complexes reconstitute a functional "Ca2+ nanodomain" where Ca2+ influx through the Cav channel activates BKCa in the physiological voltage range with submillisecond kinetics. Complex formation with distinct Cav channels enables BKCa-mediated membrane hyperpolarization that controls neuronal firing pattern and release of hormones and transmitters in the central nervous system.

1 Institute of Physiology, University of Freiburg, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany.
2 Logopharm GmbH, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany.
3 Division of Molecular and Cellular Pharmacology, Medical University Innsbruck, Peter-Mayr-Strasse 1, A-6020 Innsbruck, Austria.
4 Institute of Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25,79104 Freiburg, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. Email: bernd.fakler{at}physiologie.uni-freiburg.de (B.F.); u.schulte{at}logopharm.com (U.S.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Repolarizing Responses of BKCa-Cav Complexes Are Distinctly Shaped by Their Cav Subunits.
H. Berkefeld and B. Fakler (2008)
J. Neurosci. 28, 8238-8245
   Abstract »    Full Text »    PDF »
M2 Muscarinic Receptors Induce Airway Smooth Muscle Activation via a Dual, G{beta}{gamma}-mediated Inhibition of Large Conductance Ca2+-activated K+ Channel Activity.
X.-B. Zhou, I. Wulfsen, S. Lutz, E. Utku, U. Sausbier, P. Ruth, T. Wieland, and M. Korth (2008)
J. Biol. Chem. 283, 21036-21044
   Abstract »    Full Text »    PDF »
NMR Analysis of KChIP4a Reveals Structural Basis for Control of Surface Expression of Kv4 Channel Complexes.
J. Schwenk, G. Zolles, N. G. Kandias, I. Neubauer, H. Kalbacher, M. Covarrubias, B. Fakler, and D. Bentrop (2008)
J. Biol. Chem. 283, 18937-18946
   Abstract »    Full Text »    PDF »
Ca2+ microdomains near plasma membrane Ca2+ channels: impact on cell function.
A. B. Parekh (2008)
J. Physiol. 586, 3043-3054
   Abstract »    Full Text »    PDF »
A Close Association of RyRs with Highly Dense Clusters of Ca2+-activated Cl- Channels Underlies the Activation of STICs by Ca2+ Sparks in Mouse Airway Smooth Muscle.
R. Bao, L. M. Lifshitz, R. A. Tuft, K. Bellve, K. E. Fogarty, and R. ZhuGe (2008)
J. Gen. Physiol. 132, 145-160
   Abstract »    Full Text »    PDF »
Voltage-Gated Ion Channels in Human Pancreatic {beta}-Cells: Electrophysiological Characterization and Role in Insulin Secretion.
M. Braun, R. Ramracheya, M. Bengtsson, Q. Zhang, J. Karanauskaite, C. Partridge, P. R. Johnson, and P. Rorsman (2008)
Diabetes 57, 1618-1628
   Abstract »    Full Text »    PDF »
Neurotensin Enhances GABAergic Activity in Rat Hippocampus CA1 Region by Modulating L-Type Calcium Channels.
S. Li, J. D. Geiger, and S. Lei (2008)
J Neurophysiol 99, 2134-2143
   Abstract »    Full Text »    PDF »
Dendritic Excitability and Synaptic Plasticity.
P. J. Sjostrom, E. A. Rancz, A. Roth, and M. Hausser (2008)
Physiol Rev 88, 769-840
   Abstract »    Full Text »    PDF »
Regulation of synaptic signalling by postsynaptic, non-glutamate receptor ion channels.
B. L. Bloodgood and B. L. Sabatini (2008)
J. Physiol. 586, 1475-1480
   Abstract »    Full Text »    PDF »
Local Ca2+ Influx through Ca2+ Release-activated Ca2+ (CRAC) Channels Stimulates Production of an Intracellular Messenger and an Intercellular Pro-inflammatory Signal.
W.-C. Chang, J. Di Capite, K. Singaravelu, C. Nelson, V. Halse, and A. B. Parekh (2008)
J. Biol. Chem. 283, 4622-4631
   Abstract »    Full Text »    PDF »
From the Cover: Cytoplasmic BKCa channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons.
T. J. Bell, K. Y. Miyashiro, J.-Y. Sul, R. McCullough, P. T. Buckley, J. Jochems, D. F. Meaney, P. Haydon, C. Cantor, T. D. Parsons, et al. (2008)
PNAS 105, 1901-1906
   Abstract »    Full Text »    PDF »
The {beta}1 Subunit of L-Type Voltage-Gated Ca2+ Channels Independently Binds to and Inhibits the Gating of Large-Conductance Ca2+-Activated K+ Channels.
S. Zou, S. Jha, E. Y. Kim, and S. E. Dryer (2008)
Mol. Pharmacol. 73, 369-378
   Abstract »    Full Text »    PDF »
Differential regulation of action potential firing in adult murine thalamocortical neurons by Kv3.2, Kv1, and SK potassium and N-type calcium channels.
M. R. Kasten, B. Rudy, and M. P. Anderson (2007)
J. Physiol. 584, 565-582
   Abstract »    Full Text »    PDF »
Patch-Clamp Analysis of Gene-Targeted Vomeronasal Neurons Expressing a Defined V1r or V2r Receptor: Ionic Mechanisms Underlying Persistent Firing.
K. Ukhanov, T. Leinders-Zufall, and F. Zufall (2007)
J Neurophysiol 98, 2357-2369
   Abstract »    Full Text »    PDF »
Presynaptic Ca2+/Calmodulin-Dependent Protein Kinase II Modulates Neurotransmitter Release by Activating BK Channels at Caenorhabditis elegans Neuromuscular Junction.
Q. Liu, B. Chen, Q. Ge, and Z.-W. Wang (2007)
J. Neurosci. 27, 10404-10413
   Abstract »    Full Text »    PDF »
BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells.
N. Gu, K. Vervaeke, and J. F. Storm (2007)
J. Physiol. 580, 859-882
   Abstract »    Full Text »    PDF »
T-Type and L-Type Ca2+ Conductances Define and Encode the Bimodal Firing Pattern of Vestibulocerebellar Unipolar Brush Cells.
M. A. Diana, Y. Otsu, G. Maton, T. Collin, M. Chat, and S. Dieudonne (2007)
J. Neurosci. 27, 3823-3838
   Abstract »    Full Text »    PDF »
Co-assembly of N-type Ca2+ and BK channels underlies functional coupling in rat brain.
D. J. Loane, P. A. Lima, and N. V. Marrion (2007)
J. Cell Sci. 120, 985-995
   Abstract »    Full Text »    PDF »
Dopamine D1/5 Receptor-Mediated Long-Term Potentiation of Intrinsic Excitability in Rat Prefrontal Cortical Neurons: Ca2+-Dependent Intracellular Signaling.
L. Chen, J. D. Bohanick, M. Nishihara, J. K. Seamans, and C. R. Yang (2007)
J Neurophysiol 97, 2448-2464
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)