2008 Discussions - Calmodulin Modulation of Ion Channels
Co-sponsored by the Biophysical Society and the Office of Rare Diseases (ORD), NIEHS, NIH, with additional support from GlaxoSmithKline
Meeting Summary, January 2009
Organizing Committee:
Nikolai M. Soldatov, NIA, NIH, Chair
Mark E. Anderson, University of Iowa
David L. Armstrong, NIEHS, NIH
Lutz Birnbaumer, NIEHS, NIH
William A. Catterall, University of Washington
Susan L. Hamilton, Baylor College of Medicine
Geoffrey S. Pitt, Duke University
Joerg Striessnig, University of Innsbruck
Richard W. Tsien, Stanford University
David T. Yue, Johns Hopkins University
Ion channels are principal molecular determinants responsible for many vital functions including cell excitability, signal transduction, excitation-contraction coupling, secretion, and even transcription. Calmodulin is the prototypic calcium-sensing protein, and in the past decade it has become especially clear that calmodulin interacts with a remarkably large (and growing) number of ion channels, sometimes with yet unknown functional consequences. The fundamental role of calmodulin in signal transduction requires understanding of the underlying mechanisms, molecular determinants, and functional links.
The 2008 Discussions will address the regulatory roles of calmodulin in ion channel function with a focus on mechanisms of modulation, molecular determinants, structural principles of organization, and mediated signal transduction events. The Meeting will culminate with the session honoring Professor Harald Reuter's remarkable career in science and will be devoted to summarizing the results of 10 years of research in calmodulin modulation of ion channels.
The meeting takes place over a three-and-a-half-day period, with talks in the morning and evening, and the afternoons set aside for informal interactions. The Organizing Committee will announce if it can offer tentative partial support to speakers, but the amount will be decided at the time of the Meeting or shortly before, based on available funds and the individual requests.
The Meeting will be organized in six sessions. The presentations (15 minutes each) by leading experts in the fields will set the stage for the discussions during which the participants will exchange their results and ideas. This exchange also includes an afternoon poster session on the main topics of the meeting. The Chairs organize and moderate the discussions.
Thursday, October 30, 2008
3:00 PM Check-In
5:00 PM Reception
6:00 PM Dinner
7:30 – 9:00 PM
Ten Years of Calmodulin Research in Ion Channels: The Past and the Future
A Special Event Session Honoring Professor Harald Reuter's Remarkable Career in Science
Nikolai M Soldatov, NIA, NIH, Introduction
7:45 PM
Chairs: Harald Reuter, University of Bern, Switzerland, and Richard W. Tsien, Stanford University
In this opening session of the Meeting, discussion will focus on where we stand regarding the many established facts and loose ends of calmodulin’s functional significance in ion channel regulation.
Speakers: Lutz Birnbaumer, NIEHS, NIH
William A. Catterall, University of Washington
Richard W. Tsien, Stanford University
Friday, October 31, 2008
7:30 – 8:30 AM Breakfast
9:00 AM General Introduction
Lutz Birnbaumer, NIEHS, NIH
9:15 AM – Noon
Session 1. Mechanisms of Modulation of Ion Channels by Calmodulin
Chairs: Lutz Birnbaumer, NIEHS, NIH, and William A. Catterall, University of Washington
Issues and overview: Modulation of ion channels by calmodulin has been a focus in the investigation of calcium and calcium-dependent potassium channels for the last 10 years. However, new principles of modulation of other channels and new roles emerged recently. The speakers will address specific questions related to these recent discoveries on the issues listed below.
9:15 AM
L-Type Calcium Channels: Overview of What We Know and What We Need to Know
Mark E. Anderson, University of Iowa
9:45 AM
Calmodulin-dependent Regulation of CaV1.2 through Reversible Protein Phosphorylation
David L. Armstrong, NIEHS, NIH
Discussion: Franz Hofmann, Technische Universitaet Muenchen, Germany
10:15 AM Coffee Break
10:30 AM
K Channels and Calmodulin
Yoshihisa Kurachi, Osaka University, Japan
Discussion: John P. Adelman, Vollum Institute, and William N. Zagotta, HHMI, University of Washington
11:00 AM
Cav1.4 Channel
Joerg Striessnig, University of Innsbruck, Austria
Discussion: Christian Wahl, Ludwig-Maximilians Universitaet Muenchen, Germany
11:30 AM
Calcium Channel, Calmodulin, and Signaling to the Nucleus
Richard W. Tsien, Stanford University
12:00 – 1:00 PM Lunch
2:00 – 4:00 PM Poster Session
6:00 – 7:00 PM Dinner
Friday Evening, October 31, 2008
7:30 – 9:45 PM
Session 2. Regulation of Neuronal Channels
Chairs: Franz Hofmann, Technische Universitaet Muenchen, Germany, and Joerg Striessnig, University of Innsbruck, Austria
7:30 PM
Calcium Channels and Short-Term Synaptic Plasticity
William A. Catterall, University of Washington
8:00 PM
Calmodulin Regulation of Neuronal Ion Channels
Geoffrey S. Pitt, Duke University
8:30 PM Coffee Break
8:45 PM
Characterization of the CaMKII Activation of the Chloride Channel ClC-3, which in Neurons Modulates Synaptic Strength at Glutamatergic Synapses
Deborah Nelson, University of Chicago
9:15 PM
Mechanisms of RGK GTPase Inhibition of CaV Channels
Henry M. Colecraft, Columbia University
Discussion: Ilya Bezprozvanny, University of Texas Southwestern Medical Center at Dallas, and Nathan Dascal, University of Tel Aviv, Israel
Saturday, November 1, 2008
7:30 – 8:30 AM Breakfast
9:00 AM – Noon
Session 3. Molecular Determinants
Chairs: John P. Adelman, Vollum Institute, and David T. Yue, Johns Hopkins University
Issues: Calmodulin binds to the channels in a calcium-dependent manner and with different lobes. What do we know about common and specific patterns of these interactions? How do other molecular parts affect these interactions? How many calmodulins are interacting with a single channel? Do accessory subunits affect calmodulin regulation? What could be the role of channels clustering?
9:00 AM
SK Channels and Calmodulin
John P. Adelman, Vollum Institute
9:30 AM
Cav1 and Cav2 Channels and Calmodulin
David T. Yue, Johns Hopkins University
10:00 AM
Calcium-Dependent Inactivation is Mediated by Multiple Determinants
Nikolai M. Soldatov, NIA, NIH
Discussion: Veit Flockerzi, University of Saarland, Homburg, Germany; Joel Nargeot, Institut de Génétique Humaine, CNRS, Montpellier, France; and Qi Zong Lao, NIA, NIH
10:30 AM Coffee Break
10:45 AM
L-Channel N-Tail: Modulation by Calmodulin
Nathan Dascal, Tel Aviv University, Israel
Discussion: Martin Biel, Ludwig-Maximilians Universitaet Muenchen, Germany, and David T. Yue, Johns Hopkins University
11:15 AM
Mechanism of Ca2+/Calmodulin Regulation of TRP Channels
Sharona E. Gordon, University of Washington
11:45 AM
Calcium/Calmodulin-mediated Inhibition of Gap Junction
Jenny J. Yang, Georgia State University
Discussion: James Putney, NIEHS, NIH
12:00 – 1:00 PM Lunch
Saturday Afternoon, November 1, 2008
2:30 – 4:15 PM
Session 4. A More General Picture: Non-Channel Calmodulin
Chairs: Gerhard Meissner, University of North Carolina, Chapel Hill, and M. Neal Waxham, University of Texas Houston Medical School
Questions: Is calmodulin sequestered in cells and in what form? Is it freely available to the signaling or does its availability direct the signaling event? How mobile is calmodulin once it is released at some point in the cytoplasm? Does the concentration of calmodulin change during the cell cycle, in evolution or during development? Molecular motors related to calmodulin and their signaling role.
2:30 PM
Limiting Calmodulin Revealed by Image Correlation Spectroscopy
M. Neal Waxham, University of Texas Houston Medical School
3:00 PM Coffee Break
3:15 PM
Dynamic Ca-CaM Signals in Cardiac Myocytes Targeting CaMKII and Calcineurin
Donald M. Bers, University of California, Davis
3:45 PM
Alternatively Spliced Calmodulin-2 was Found by the Yeast-2-Hybrid Technique as Putative Partner of Cav2.3, and is Expressed in Two Human Cell Lines
Toni Schneider, University of Cologne, Germany
Discussion: Deborah Nelson, University of Chicago
6:00 – 7:00 PM Dinner
Saturday Evening, November 1, 2008
7:10 – 9:25 PM
Session 5. Signal Transduction Events Mediated by Calmodulin-Ion Channels Coupling
Chairs: Mark E. Anderson, University of Iowa, and William N. Zagotta, HHMI, University of Washington
Issues: Among many processes mediated by calmodulin, the regulation of intracellular calcium release and transcription regulation are the focus of recent studies. Are calcium sensors available to the cytosolic calcium, e.g., released from the SR? What do we know about the organization of the underlying events? How is the coupling of the ion channel activity mediated to alter signaling? What may be the role of calmodulin-like proteins? These questions will be addressed in the topics listed below.
1. Excitation-Contraction Coupling
7:10 PM
Unresolved Issues of Calmodulin Modulation of Ryanodine Receptors
Gerhard Meissner, University of North Carolina, Chapel Hill
Discussion: Susan L. Hamilton, Baylor College of Medicine
2. Transcriptional Events Mediated by Calcium Channels and Calmodulin
7:40 PM
Transcription Factor Activity of the L-type Calcium Channel
Ricardo E. Dolmetsch, Stanford University
8:10 PM Coffee Break
8:25 PM
Calmodulin/L-type Calcium Channel-mediated Activation of CREB-dependent Transcription in Nuclear Microdomains
Evgeny Kobrinsky, NIA, NIH
8:55 PM
CaBP1 and CaBP4 Modulation of Cav1 Channels: Regulation of Calcium Feedback to Cav2.1 Channels by Parvalbumin/Calbindin
Amy Lee, Emory University
Discussion: Toni Schneider, University of Cologne, Germany
Sunday, November 2, 2008
7:30 – 8:30 AM Breakfast
9:00 – 11:00 AM
Session 6. Structural Principles of Organization
Chair: Daniel L. Minor, Jr., University of California, San Francisco
Issues: What do we know about the molecular organization of calmodulin binding sites? How does calcium affect the structure of calmodulin in binding sites?
9:00 AM
Structural and Mechanistic Studies of Calmodulin Regulation of Voltage-gated Calcium Channels
Daniel L. Minor, Jr., University of California, San Francisco
9:20 AM
Structural Studies of CaM Interaction with L-type Calcium Channels and RyRs
Ashraf Kitmitto, University of Manchester, United Kingdom
9:40 AM Coffee Break
10:00 AM
Molecular Recognition by Calmodulin: Balancing Binding and Bending
Madeline A. Shea, University of Iowa
Discussion: John P. Adelman, Vollum Institute
10:20 AM
Meeting Wrap Up
Summary of the Meeting
David T. Yue, Johns Hopkins University
A word on behalf of the Organizing Committee
Nikolai M. Soldatov, NIA, NIH
Closing Remarks
Harald Reuter, University of Bern, Switzerland