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The discovery opens the possibility of designing new types of drugs against conditions such as epilepsy. The results are presented in the journal Science Advances. The answer is that they all affect the ability of nerves to transmit electrical impulses by affecting the ion channels in nerves. Ion channels are small openings in the cell membrane of nerves that open and close like doors, in order to allow electrically charged ions to enter or exit.
When enough ions have flowed into the nerve cell, an electrical impulse is released and transmitted along the nerve. Sometimes, however, it becomes far too easy for an electrical impulse to be released. Increased electrical excitability of nerves lies behind such conditions as epileptic seizures, disturbances in heart rhythm, and the experience of pain. The anti-epileptic medication currently in use, and the animal toxins mentioned above, reduce electrical excitability by closing a certain type of ion channel.
All such previously known molecules bind to locations at the ion channel itself. These binding sites are generally surrounded by water. In contrast, the cell membrane that the ion channel passes through is built from a bilayer of lipids, which are a form of fat that repels water-soluble substances. This is a fundamentally different type of binding site.
One interesting question is whether we have naturally occurring molecules in the body that bind to ion channels in the same way. The researchers who have conducted the study have previously discovered that naturally occurring resin acids can regulate an ion channel that allows the passage of potassium ions.
Resin acids are found in the resin from conifers, such as the Swedish pine tree. Some of them influence the voltage dependence of the ion channel, and we believe that it will be possible to exploit this mechanism in future drugs," says Nina Ottosson, principal research engineer in the Department of Clinical and Experimental Medicine, and leading author of the article.
The researchers have investigated the effect of the substances on a potassium ion channel from fruit flies. This ion channel is essentially the same in fruit flies and in humans. When the researchers wanted to examine in detail how the substances affect the ion channel, they discovered the new binding site. They have also identified a strong relationship between the chemical structure of the substances and their effect on the ion channel.
Our findings provide information about how we can modify substances to make them as effective as possible," says Fredrik Elinder. Approximately one third of people with epilepsy still experience seizures even when receiving treatment, and currently available anti-epileptic drugs often have side effects such as tiredness and dizziness. The researchers hope that the drug-like substances can be developed into new drugs against epilepsy.
Some of the researchers have filed a patent application coupled to this study. Note: Content may be edited for style and length. Journal Reference: Nina E. A drug pocket at the lipid bilayer—potassium channel interface.
Science Advances, ; 3 10 : e DOI:
New method to dampen nerve signals
D from Paul Sabatier University Toulouse. Bernard Attali is Full Professor at the Sackler Medical School in Tel Aviv University, where his research aims at elucidating the structural, biophysical and physiological attributes of potassium channels. Bernard Attali contributed to the characterization of Kv7 potassium channels, whose mutations in humans lead to cardiac arrhythmias, epilepsy or autism disorders. He also showed that M-current inhibition in hippocampal neurons triggers intrinsic and synaptic homeostasis plasticity. He has published so far more than papers in peer-reviewed international journals. His research is focused on sensory neuron biology, with an emphasis on sensory transduction mechanisms and on the pathophysiological mechanisms of chronic pain. Current projects are focused on the basic physiology of TRP channels, diabetic and chemotherapy-induced neuropathy, and translational studies of complex regional pain syndrome CRPS and fibromyalgia.
Personporträtt: Fredrik Elinder
Abstract abstract Voltage-gated ion channels respond to changes in the transmembrane voltage by opening or closing their ion conducting pore. The positively charged fourth transmembrane segment S4 has been identified as the main voltage sensor, but the mechanisms of coupling between the voltage sensor and the gates are still unknown. Obtaining information about the location and the exact motion of S4 is an important step toward an understanding of these coupling mechanisms. In previous studies we have shown that the extracellular end of S4 is located close to segment 5 S5.
FREDRIK ELINDER PDF
Gojinn A new report highlights major structural deficiencies in the police that lead to mistakes and the use of excessive force. International invited speakers and researchers from several Wallenberg centres presented and discussed research results at the third symposium arranged by the Wallenberg Centre for Molecular Medicine at LiU. Head of Department, Professor. Fredrik Elinder Once a week the kitchens at Campus Valla operate at full pressure. High levels of lutein are found in dark green vegetables, and researchers at LiU have compared different ways of preparing fresh spinach in order to maximise the levels of lutein in finished food.