Biological complexity: mechanism of Big Potassium ion pore (Introduction)

by David Turell , Saturday, August 25, 2018, 20:26 (2282 days ago) @ David Turell

This is the way electricity is able to move quickly in an out of the neuron body:

https://www.sciencedaily.com/releases/2018/08/180824090613.htm

"Chen says, "The main way for the nervous system to send electrical signals is by opening and closing potassium and other ion channels that help regulate neuronal firing and neurotransmitter release. These Big Potassium channels are central for coupling electrical signaling to calcium-mediated events such as muscle contraction and neural excitation," and how blood pressure is regulated, for example.

"'These BK channels contain extra-large pores, so they can sustain very large current, which lets the cell respond faster," he adds. BK channels play an important role in many health conditions such as hypertension, epilepsy, autism and mental retardation.

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"The gate mechanism in BK channels they have been studying is "drastically different from what has been observed in other ion channels," the authors point out. "We believe that this work represents a paradigm shift in our thinking of regulation and gating of BK channels," and is "one of the first few examples of a true 'hydrophobic gate,' where the barrier to ion permeation arises directly from dewetting transitions."

"Hydrophobic dewetting refers to a phenomenon similar to the way water placed on an oily surface beads to form droplets. Initiation of dewetting transitions in BK channels requires changes in the pore shape and surface hydrophobicity driven by calcium binding. When the BK pore is oily, the water forms a vapor phase that acts like a barrier and prevents all ions from entering, Chen says. "Nothing gets through."

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"He says, "If you think about why nature might want to use a vapor barrier where there is a big pore that has to carry a lot of electrical current, to apply a physical barrier you would need a protein structural re-arrangement which would probably be either too big or too slow, or both. In a way, nature is really clever in using this hydrophobic dewetting phenomenon to create a sensitive and fast gate. We were actually really surprised to see that the changes in pore shape and surface properties are relatively small and subtle, but they have big consequences on its hydration properties."

"Further, Chen says, "In terms of understanding how the channel is gated, now we know more and it gives us a strong basis to see how other domains of BK channels talk to the pore and how the membrane voltage, calcium gradient, and a few other chemical signals control the state of the pore. In principle, that knowledge should be useful in developing new therapies and strategies in targeting the channel.'"

Comment: Here is another highly complex mechanism that requires design all at once to create controls over the speed of ions moving. Think about how quickly you move when mistakenly touching a hot stove. Pore size will always be controlled by feedback loops which also have to be designed for they involve several steps.