Ion channels in the cell membrane enable cells to communicate with their environment and are therefore of vital importance. The MDC researchers have developed a system which for the first time allows the targeted, long-lasting investigation of ion channel function in mammals and also the blockade of the ion channels with neurotoxins.
In transgenic mice they succeeded in blocking chronic pain by introducing a toxin gene into the organism (Nature Method, doi:10.1038/NMETH.1425)*.
There are approximately 500 species of cone snails, each producing 50 – 200 different conotoxins. A similar number of peptide toxins are produced by snakes, spiders, sea anemones, scorpions and other venomous animals. The animals use the neurotoxins to paralyze their prey.
Scientists estimate that more than 100,000 neurotoxins exist. They have become a topic of enormous research interest: Using neurotoxins researchers can target different ion channels, receptors and other signaling molecules and characterize their physiological function.
This kind of research can also give them insight into disease processes and eventually help them to find new therapies to eventually block hyperactive ion channels. For instance, a compound (Ziconotide) based on the toxin of a cone snail is already used to treat severe chronic pain in patients.
Dr. Ibañez-Tallon’s research group is concentrating on two ion channels in the membrane of neurons which are activated by electric stimulation (action potential). Once activated, they allow the influx of calcium ions into the neuron, and the cell then releases chemicals (neurotransmitters), which send the signal to the next neuron.
During the last decades soluble neurotoxins have greatly helped in the characterization of ion channels and receptors because of their ability to specifically bind and inhibit these channels. However, soluble neurotoxins can only be applied for limited time, and their activity cannot be directed to specific cells.
Sebastian Auer, Annika S. Stürzebecher and Dr. Ibañez-Tallon managed to circumvent this problem with genetic engineering. Using lentiviruses they developed a shuttle to deliver the genes of cone snail and spider toxins into the neurons. The result: The neurons now long-lastingly produce toxins which directly bind to the calcium ion channels the researchers want to investigate. This was the first step – the targeted and long-lasting binding of the toxins to a specific ion channel in the cell culture.
Secondly, the researchers were able to demonstrate that with their tool they can also express toxin genes in animals in a targeted way and also lastingly characterize ion channels. In transgenic mice they were able to block certain calcium ion channels with their toxins and thus block chronic pain.
*Silencing neurotransmission with membrane-tethered toxins
Sebastian Auer1,4, Annika S Stürzebecher1,4, René Jüttner2, Julio Santos-Torres1, Christina Hanack1, Silke Frahm1, Beate Liehl1 & Inés Ibañez-Tallon1
1Molecular Neurobiology group and 2Developmental Neurobiology group, Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany. 3Present address: Novartis Pharma AG, Basel, Switzerland. 4These authors contributed equally to this work. Correspondence should be addressed to I.I.-T. (email@example.com).Barbara Bachtler
Barbara Bachtler | EurekAlert!
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences