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New studies reveal downstream processes of ion channel inactivation

03.03.2010
Two studies by researchers at The Johns Hopkins University School of Medicine reveal new details of the mechanisms of ion channel inactivation. The papers appear in the March issue of The Journal of General Physiology (www.jgp.org).

After opening, many ion channels spontaneously close by inactivation, a process distinct from that involved in opening. The inactivation of channels is important for a variety of biological processes, including the timing of action potentials and the control of calcium permeability, which affects many aspects of intracellular signaling. Although the events of Ca2+-dependent inactivation (CDI) and voltage-dependent inactivation (VDI) have been unveiled in the past decade, the downstream mechanisms remained unclear.

Tadross et al. studied both CDI and VDI in Cav1.3 channels and showed them to differ not only in their initiation mechanisms but also in their distinct molecular endpoints. For CDI, a clear pattern emerges: activation-enhancing mutations proportionately weaken inactivation, supporting the idea that CDI reduces channel permeability by allosteric hindrance of the activation gate. For VDI, the data implicate a "hinged lid–shield" mechanism, similar to a hinged-lid process, with a previously unrecognized feature, a "shield" in Cav1.3 channels that is specialized to repel lid closure.

In a Commentary accompanying the papers, Jianmin Cui (Washington University, St. Louis) examines the mechanisms of inactivation and provides context for the importance of the new findings by Tadross et al.

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»CDI »Cav1 »Gen FTO »JGP »Physiology »VDI »biological process

About The Journal of General Physiology

Founded in 1918, The Journal of General Physiology (JGP) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists. JGP content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit www.jgp.org.

Cui, J. 2010. J. Gen. Physiol. doi:10.1085/jgp.201010421.
Tadross, M.R., et al. 2010. J. Gen. Physiol. doi:10.1085/jgp.200910308.
Tadross, M.R., and D.T. Yue. 2010. J. Gen. Physiol. doi:10.1085/jgp.200910309.

Rita Sullivan | EurekAlert!
Further information:
http://www.rupress.org
http://www.jgp.org

Further reports about: CDI Cav1 Gen FTO JGP Physiology VDI biological process

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