#potassium channel

[bpod-bpod]

Weary Worms

<

Melatonin is the brain hormone that makes our eyelids droop and brings on the Zs. Some people take it in pill form to help combat jet lag or to get a good night’s sleep, but how the hormone actually induces sleep is largely a mystery. To learn more about the molecular mechanisms of melatonin researchers are studying how the hormone induces sleep in the nematode worm Caenorhabditis elegans (pictured). Yes, worms sleep too! The scientists have found that when melatonin binds to its receptor (green) on the surface of brain cells, it activates a particular potassium channel, which in turn switches off communication between the cells. Worms that lacked either the melatonin receptor or the channel had trouble sleeping. It seems, then, that brain cells, much like kids at a sleepover, need to quit yapping to get to sleep. And, melatonin, much like a strict parent, enforces that silence.

Written by Ruth Williams

Image from work by Longgang Niu and colleagues

Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, USA

Image copyright held by the original authors

Research published in Proceedings of the National Academy of Science (PNAS), October 2020

You can also follow BPoD on Instagram, Twitter and Facebook

[neurosciencenews]

How Excited Neurons Settle Down

Within the brain, some neurons fire off hundreds of signals per second, and after ramping up for such a barrage, they need to relax and reset. A particular type of ion channel helps bring them down, ensuring these cells don’t get overstimulated—a state that potentially can lead to severe epileptic seizures, among other problems.

The research is in Nature. (full access paywall)

Research: “Cryo-electron microscopy structure of the Slo2.2 Na+-activated K+ channel” by Richard K. Hite, Peng Yuan, Zongli Li, Yichun Hsuing, Thomas Walz & Roderick MacKinnon in Nature doi:10.1038/nature14958

Image: Potassium’s path: The single large protein constituting the Slo2.2 channel has four-fold symmetry, shown above from the side. To leave the cell, a potassium ion must first pass through the gating ring (lower half) of the channel, then through the membrane-spanning domain (top half). Image adapted from the Rockefeller University press release.

[currentsinbiology]

Studying dynamics of ion channels

Despite a large body of work, the exact molecular details underlying ion selectivity and transport of the potassium channel remain unclear. "Since conventional methods, such as X-ray crystallography, capture only averaged frozen structures, it is not possible to investigate how the dynamic of the protein could be involved in key aspects of their function", explains physicist Alipasha Vaziri, a joint group leader at the Max F. Perutz Laboratories (MFPL) and the Institute of Molecular Pathology (IMP) and head of the research platform "Quantum Phenomena & Nanoscale Biological Systems" (QuNaBioS) of the University of Vienna.

Vaziri's team, together with researchers at the Institute for Biophysical Dynamics (University of Chicago), have now used infrared (IR) spectroscopy coupled with molecular dynamic-based simulations of the obtained spectra to investigate the subtlest changes in the shape of the KcsA potassium channel that are induced by binding either potassium or the only 0.04 nanometers smaller sodium ion. This combination proved to be a powerful tool to disentangle convoluted IR spectra - which contain contributions from the whole protein - by assigning each part of the spectrum to the amino acids that contribute to it.

Publication in the Journal of Physical Chemistry B: Paul Stevenson, Christoph Götz, Carlos R. Baiz, Jasper Akerboom, Andrei Tokmakoff and Alipasha Vaziri: Visualizing KcsA Conformational Changes upon Ion Binding by Infrared Spectroscopy and Atomistic Modeling. In: The Journal of Physical Chemistry B (April 2015). DOI: http://dx.doi.org/10.1021/acs.jpcb.5b02223

Caption: Location of the potassium channel KcsA in the cell membrane of bacteria. The schematic illustration on the right shows the changes in strength and direction of vibrational coupling inside the filter depending on the ion species, as found by the study. Credit: Copyright: David S. Goodsell & RCSB Protein Data Bank

[currentsinbiology]

Tarantula toxin is used to report on electrical activity in live cells

A novel probe that reports on the electrical activity of cells, made by fusing tarantula toxin with a fluorescent compound, is described in a paper by scientists from the University of California, Davis; the Neurobiology course at the Marine Biological Laboratory (MBL); and Lawrence Berkeley National Laboratory.

The probe takes advantage of the potent ability of tarantula toxin to bind to electrically active cells, such as neurons, while the cells are in a resting state. The team discovered that a trace amount of toxin combined with a fluorescent compound would bind to a specific subset of voltage-activated proteins (Kv2-type potassium ion channels) in live cells. The probe lights up cell surfaces with this ion channel, and the fluorescent signal dims when the channel is activated by electrical signals.

This is the first time that researchers have been able to visually observe these ion channels "turning on" without first genetically modifying them. All that is required is a means to detect probe location, suggesting that related probes could potentially one day be used to map neural activity in the human brain.

Caption: The movie is quantitative imaging of cells with potassium channels, bathed in dilute fluorescent tarantula toxin. Pixel color indicates intensity of tarantula toxin concentration. The circular shapes are cell surfaces, illuminated by tarantula toxins bound to potassium channels. The cell on the right is electrically stimulated to the indicated voltages. The cells on the left remain at constant resting voltage. Intensity change reports activation of potassium channels. At -100 mV channels are at rest. During stimulus to 0 mV channels activate and fluorescence decreases as tarantula toxins fall off of potassium channels. Upon return to -100 mV, tarantula toxins find the resting channels again.

Credit: Recorded by Kenneth Eum, Lillian Patrón, and Christophe Dupré in the MBL Neurobiology course. Video courtesy of Jon Sack, UC-Davis.

[currentsinbiology]

Water molecules control inactivation and recovery of potassium channels (EurekAlert)

Just 12 molecules of water cause the long post-activation recovery period required by potassium ion channels before they can function again. Using molecular simulations that modeled a potassium channel and its immediate cellular environment, atom for atom, University of Chicago scientists have revealed this new mechanism in the function of a nearly universal biological structure, with implications ranging from fundamental biology to the design of pharmaceuticals. Their findings were published online July 28 in Nature.

"Our research clarifies the nature of this previously mysterious inactivation state. This gives us better understanding of fundamental biology and should improve the rational design of drugs, which often target the inactivated state of channels" said Benoît Roux, PhD, professor of biochemistry and molecular biology at the University of Chicago.

Caption: Depiction of simulated potassium channel and surrounding environment. Potassium ions (green) are unable to pass through because water molecules (red and white) are present inside the protein, locking the channel into an inactivated state.

Credit: Benoit Roux, University of Chicago