Good neighbours
Physiologists from the University of Freiburg demonstrate why ion channels open quickly in the cell membranes of muscles and nerves
Structure model of a protein supercomplex with BK channels | Ion channels are crucial for signal transduction between and within cells - without these proteins, cells would not be able to communicate. These channels are located in the cell membrane and conduct ions in response to external stimuli that changes their structure and thereby open the channel pore. Only a few channels can accept more than one stimulus, and one of these is the BK channel, which is triggered by both transmembrane voltage and intracellular calcium. Prof Dr Bernd Fakler, from the Institute of Physiology of the University of Freiburg and a member of BIOSS Centre for Biological Signalling Studies, and Dr Henrike Berkefeld, also from the Institute of Physiology, successfully demonstrated the conditions under which BK channels open in nerve and muscle cells. The team of researchers was able to solve the question of whether or not the ion channels in these cells utilise both voltage and calcium, or if they react to just one of these stimuli. According to their findings, BK channels are primarily activated by calcium under cellular conditions and their activity is increased by neighbouring calcium channels. The researchers recently published the results of their study in the Journal of Neuroscience. |
Different proteins can be co-assembled into protein supercomplexes, as also happens with BK channels and voltage-gated calcium channels. In such supercomplexes formed by direct protein-protein interactions, BK and calcium channel proteins form a symbiotic relationship. Thus, voltage changes across the membrane first lead to opening of the calcium channels, as discovered by Berkefeld and Fakler. This allows calcium ions to enter the cell which subsequently open the BK channels. Consequently, the calcium ions act as ligands, meaning they attach to the BK protein and activate it. Because BK channels are not directly affected by voltage, they function like ion channels that are influenced purely by ligands under cellular conditions.
In protein complexes with calcium channels BK channels are also activated markedly faster than they would in the absence of these partners. If a BK channel is exposed to calcium alone, it will eventually open after a delay. This delay can be problematic or even harmful for nerve signalling. As Fakler and Berkefeld have demonstrated, calcium channels help their neighbouring BK channels in two ways: They supply them with activating ligands and they accelerate their efficiency.
Original Publication:
Ligand-Gating by Ca2+ Is Rate Limiting for Physiological Operation of BKCa Channels
Berkefeld H, Fakler B.
J Neurosci. 2013 Apr 24;33(17):7358-67