Without a central nervous system, you would be dead. But how does the nervous system work? Nerves are composed of cells called neurons that rely on communication – signals they send and receive. Those signals come into a neuron by means of channels in the cell membrane. Cells have a variety of channels in their membranes. Some of the most important in neurons are the potassium channels that raise and lower the electrical voltage inside. Among these are calcium-activated potassium channels, which not only let calcium in, but export it out when the inside calcium concentration is too high. These channels make nerves communicate, make muscles work, and improve your hearing, among other things. Scientists have not understood how the inside calcium was able to activate the channel to let excess calcium back out. Now, a leading channel researcher has figured it out: the calcium binds to a gating ring inside the cell, and makes it open like a flower.
For a decade, Roderick MacKinnon’s team has been in the forefront of figuring out how these amazing gatekeepers of the cell work (see 1/17/2002, 3/12/2002, 5/29/2002, 5/01/2003, 8/05/2005, 12/02/2007). Up till now, researchers have only seen the closed state of the gating ring. MacKinnon’s team has imaged the tiny gate in the open condition for the first time, and found that looks like a flower with four petals opening up. The abstract in Nature1 says:
Here we present the Ca2+–bound conformation of the gating ring. This structure shows how one layer of the gating ring, in response to the binding of Ca2+, opens like the petals of a flower. The degree to which it opens explains how Ca2+ binding can open the transmembrane pore.
The paper includes movies of how the structure works. Sure enough, calcium ions binding to specialized pockets in the gating ring cause a conformational change that looks for all the world like flower petals opening. The four “petals” rock upward and back, widening the channel enough for ions to pass through. The action is reversible. When the calcium concentration drops again, the petals fold and the channel closes.
They used the flowery metaphor again inside the paper: “Viewing an interpolative movie in which the Ca2+–free gating ring is morphed to the Ca2+–bound gating ring, it seems that Ca2+ binding causes the N-terminal lobes of the RCK1 units to ‘open up’ on the membrane-facing surface of the gating ring in a way akin to petals opening on a flower (Supplementary Movie 1, part 1).”
One thing still remaining to understand is how the binding generates force: “Precisely how the free energy of Ca2+ binding in either the BK or MthK gating rings is transduced into mechanical work remains an important outstanding question that will require further experimental and theoretical work to understand at a deep level.”
But now, at least, we know now that your muscles, your heart, your digestive tract, your ears and your nerves operate with flower power.
1. Yuan, Leonetti, Hsiung, and MacKinnon, “Open structure of the Ca2+ gating ring in the high-conductance Ca2+–activated K+ channel,” Nature 481 (05 January 2012), pp. 94–97, doi:10.1038/nature10670.
Wonderful discoveries. Who could have imagined such things a few decades ago? Through the whole history of mankind, from the most ancient thinkers who considered the design of life, we are the ones blessed to see machinery in operation at the fundamental level of the cell and its components. The researchers imaged these things in zebrafish cells at 3.6 Angstrom resolution! (An Angstrom is about the width of a hydrogen atom, and zebrafish BK channels are 93% similar to human channels in amino acid sequence). We should be grateful to see what our predecessors could only wonder at.
Only at the end of this paper did the authors suggest that this particular eukaryotic channel with its moving parts evolved from a simpler prokaryotic channel that uses a different opening mechanism: “This comparison presents a fascinating example in which the evolution of molecular structure has given rise to new or modified mechanical properties within a class of molecules,” they said. (This is known as fact-free speculation.) The paper needed evolutionary theory like a checkpoint gate in Iraq needs a suicide bomber. Give credit to the Designer of elegant machinery, not to blind, unguided, purposeless concourses of mindless atoms. Next time you lift weights, digest a good meal, listen to music or check your heartbeat, thank God for calcium-activated potassium channels with flower-petal activation gates.