New research from Dr. Roderick MacKinnon’s Laboratory of Molecular Neurobiology and Biophysics at The Rockefeller University has determined, for the first time, the complete structure of an ion channel that plays an important role in cellular electrical signaling by sending potassium ions out of the cell at an extremely rapid rate. By revealing new insights into how the molecule works, this research leads to a deeper understanding of the link between the membrane and processes inside the cell, including calcium regulation of electrical signals, which is central to muscle contraction and neural activity. The results are described in two papers “Cryo-EM structure of the Open High-Conductance Ca2+-Activated K+ Channel” and “Structural Basis for Gating the High-Conductance Ca2+-Activated K+ Channel”) published online in Nature on December 14, 2016. Potassium channels both regulate the occurrence of electrical impulses and terminate the impulses once they are generated. One such potassium channel, known as the BK or “big potassium” channel, conducts ions up to a level 20 times that of other potassium channels. To do so, BK responds to two separate triggers—electrical activity on the cell membrane and levels of calcium—that it ties together. When BK malfunctions, cells can become too active because they can’t turn off their electrical impulses. This contributes to diseases such as hypertension, a hereditary form of asthma, and overactive bladder, in which smooth muscles in the vascular system, airway, or bladder are overactive. Dr. MacKinnon began trying to work out the structure of this channel, including the tunnel-like pore through which the ions travel, about 15 years ago; but new imaging technology has only just now made this effort feasible.
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