Breaking News
September 20, 2018 - Could Household Cleaners Make Your Kid Fat?
September 20, 2018 - Addiction nonprofit makes searching for services simple
September 20, 2018 - We are bombarded by thousands of diverse species and chemicals | News Center
September 20, 2018 - Experts to Present Prostate Cancer Advances at Patient Summit
September 20, 2018 - Alector announces initiation of Phase 1 trial of AL001 for treating frontotemporal dementia
September 20, 2018 - Pfizer’s 20vPnC vaccine receives Breakthrough Therapy designation from FDA
September 20, 2018 - Study could allow doctors to screen patients at risk from Aspergillus
September 20, 2018 - Emergex signs MoU with Brazil’s Fiocruz for development of viral vaccines
September 20, 2018 - The ‘real you’ is a myth – we constantly create false memories to achieve the identity we want
September 20, 2018 - Researchers describe cell mechanism that optimizes proteins production in stressful situations
September 20, 2018 - Cell Medica successfully doses first patient with CMD-501 targeting pediatric neuroblastoma
September 20, 2018 - Senators unveil legislation to protect patients against surprise medical bills
September 20, 2018 - Study provides insights into development of special-purpose cosmetic products
September 20, 2018 - Research shows enlarged genotype-phenotype correlation for three-base pair deletion in NF1
September 20, 2018 - DePuy Synthes introduces CONCORDE LIFT Expandable Interbody Device at EUROSPINE 2018
September 20, 2018 - Manx Telecom unveils MT clearSound that improves clarity of mobile phone calls
September 20, 2018 - Mediterranean-style diet appears to reduce stroke risk in women
September 20, 2018 - AbbVie Announces Patient-Reported Outcomes Data from Three Pivotal Phase 3 Studies of Risankizumab, Showing Significant Improvements in Health-Related Quality of Life for Patients with Psoriasis
September 20, 2018 - Characterization of pregnancy microbiome reveals variations in bacterial diversity
September 20, 2018 - New guidance for treatment of bone loss in hematologic stem cell transplant Recipients
September 20, 2018 - Experts to present research on prevention, management of dysphagia at international conference
September 20, 2018 - New study focuses on two-way gene switches controlling gene activity
September 20, 2018 - Zika virus could become a weapon against brain cancer
September 20, 2018 - Home-based video game exercises can reduce chronic low back pain in older people, study finds
September 20, 2018 - Investigators find that bile acids reduce cocaine reward
September 20, 2018 - Cannabinoid drugs reduce perceived unpleasantness of painful stimuli and increase tolerance
September 20, 2018 - Health care companies’ data could enable more accurate flu season forecasts
September 20, 2018 - Geroscience takes center stage in Journal of the American Medical Association
September 20, 2018 - Ambient Particulate Matter Linked to Emergency Asthma Care
September 20, 2018 - Patient satisfaction with plastic surgery—it’s the surgeon, not the practice
September 20, 2018 - Medicine is a team sport – and that’s exactly how it should be
September 20, 2018 - Logos Biosystems releases new electrophoretic tissue clearing system with twice the features in half the space
September 20, 2018 - Novel micro-platform reveals never-before-seen behaviors of cancer cells
September 20, 2018 - PAREXEL partners with Datavant to enhance clinical study design and generate real-world evidence
September 20, 2018 - Robert Koch Institute publishes new data on allergies, mental health problems, and accident injuries
September 20, 2018 - Study finds higher readmission rates in for-profit hospitals
September 20, 2018 - Encouraging youth to do strength-based exercises could help tackle child obesity
September 20, 2018 - Sleep apnea, congenital heart disease in hospitalized infants strongly associated with death
September 20, 2018 - Researchers find way to map mysterious content of non-coding RNA
September 20, 2018 - Air Pollutants Reach Placenta, Might Harm Fetus: Study
September 20, 2018 - Sleep apnea, congenital heart disease may be deadly mix for hospitalized infants
September 20, 2018 - My relative has cancer, should I worry? Encouraging cascade genetic testing
September 20, 2018 - Investigators determine specific treatable traits that can predict future asthma attacks
September 20, 2018 - More doctor visits can lower risk of suicide attempts in fibromyalgia patients
September 20, 2018 - Computer avatars play role in diagnosis of dementia
September 20, 2018 - Addition of CTLA4 targeted therapy to PD-1 targeted therapy may benefit patients with ovarian cancer
September 20, 2018 - ASPREE trial explores whether low dose aspirin can prolong good health in elderly people
September 20, 2018 - ATS publishes new guideline focused on weight loss strategies for sleep apnea patients
September 20, 2018 - The Current issue of “The view from here” is concerned with Drug Delivery
September 19, 2018 - Sleep apnea could favour tumor growth at young ages
September 19, 2018 - Stealth vaping fad hidden from parents, teachers
September 19, 2018 - Witnessing school violence linked to later risk of psycho-social and academic impairment
September 19, 2018 - Common household cleaners could make children overweight by changing gut microbiota
September 19, 2018 - Salk research in yeast leads to serendipitous finding about hypomyelinating leukodystrophy
September 19, 2018 - Study: Overweight or obese women may have increased risk of urinary incontinence
September 19, 2018 - Study shows how cellular waste disposal processes also promote inflammation
September 19, 2018 - New multidisciplinary microsurgery microscope, PROVIDO, introduced by Leica
September 19, 2018 - Phase 2b STORM Data Evaluating Selinexor in Patients with Penta-Refractory Multiple Myeloma Presented at the Society of Hematologic Oncology 2018 Annual Meeting
September 19, 2018 - Decisions recruiting gut feelings seen as reflection of true self, more assuredly held, study says
September 19, 2018 - How AI can improve end-of-life care
September 19, 2018 - UNIST and Ulsan initiate research collaboration to develop human organs-on-chips
September 19, 2018 - Study highlights key role of migrating shoals of fish in sustaining deep-ocean microorganisms
September 19, 2018 - Disagreeable individuals can benefit most from behaving more compassionately, finds study
September 19, 2018 - Janssen Submits New Drug Application to U.S. FDA Seeking Approval of Erdafitinib for the Treatment of Metastatic Urothelial Cancer
September 19, 2018 - Neuroplasticity is increased but dysregulated in the aging brain, study finds
September 19, 2018 - Suicide: A public health crisis
September 19, 2018 - Infants using popular anti-reflux medicines are not at increased risk of lung infections
September 19, 2018 - Stanford team will participate in NIH-funded study of tobacco policies | News Center
September 19, 2018 - Women with high levels of anti-Müllerian hormone more likely to develop breast cancer
September 19, 2018 - Researchers use larval zebrafish model to reveal role of locus coeruleus in anesthesia
September 19, 2018 - Effects of prematurity found to be more severe for the brains of males than females
September 19, 2018 - NIH funds CWRU to investigate new imaging approach for diagnosing peripheral arterial disease
September 19, 2018 - NUS researchers develop new device for quick and accurate screening of diseases
September 19, 2018 - Leading nutritionist explains about different types of iron in oral supplements
September 19, 2018 - New Crest Gum & Enamel Repair toothpaste may boost enamel repair and reverse gingivitis
September 19, 2018 - Analysis does not find any safety concerns of bivalent HPV vaccine
September 19, 2018 - Many Older Adults Transition to Long-Term Benzodiazepine Use
September 19, 2018 - Caregiving – resources – older adults: MedlinePlus Medical Encyclopedia
September 19, 2018 - Research shows that cystic fibrosis impacts growth in the womb
September 19, 2018 - Study shows how head, neck positioning affects concussion risk | News Center
Study reveals functional dynamics of ion channels

Study reveals functional dynamics of ion channels

image_pdfDownload PDFimage_print

Most ion channels are very selective about the ions, which may or may not pass through them. They may be conductive for potassium ions and non-conductive for sodium ions or vice versa. However, a number of ion channels allows for the efficient passage of both kinds of ions. How do these channel proteins accomplish this? A team of scientists around Dr. Han Sun and the research group of Professor Adam Lange at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) found the answer to this question. Their study revealed structural and dynamic differences between selective and non-selective ion channels. The scientists described their findings and conclusions in the journal Nature Communications. In non-selective channels, the selectivity filter exhibits sizeable dynamics, which are not present in selective channels. The selectivity filter of non-selective ion channels can exist in two different forms. Dependent on the state of the selectivity filter, one or the other ion type may pass.

Ion channels play prominent roles in organisms. For example, ion channels are in action when the organism registers stimuli and passes the information on to the brain in the form of electric signals. During this signal transmission, charged atoms (ions) must enter and leave the involved cells. Ions cannot permeate lipophilic cell membranes. Instead, they pass through protein channels in the cell membranes.

In many cases, the ion channels allow the passage of only one specific ion type, i.e. they may be conductive for potassium but not for sodium ions or vice versa. The selectivity filter that is the narrowest part of the channel is responsible for this ion discrimination. However, the NaK channel allows for the passage of both sodium and potassium ions. It was in the focus of the present study by FMP scientists around Dr. Han Sun and Professor Adam Lange together with colleagues in Göttingen (Germany) and Hefei (China).

Non-selective ion channels are very important in medicine.

Until now, it has remained controversial why NaK channels allow for the passage of both sodium and potassium ions. Professor Adam Lange explains: “While X-ray crystallographic images showed us the three-dimensional structure of the channel, it was difficult to explain why this channel is conductive to two different ion types with similarly high efficiency. This was particularly hard to understand because the sequence and the 3-D structure of the selectivity filter are similar to the ones in potassium selective channels.”

Scientist Dr. Han Sun added that the investigated system is a model system for several other non-selective ion channels in the human body. As she pointed out, physiologically and medically relevant in this context are the cyclic nucleotide-gated and hyperpolarization-activated cyclic nucleotide-gated channels (CNG and HCN channels): “We know that CNG channels are important for vision and smell. Dysfunctional HCN channels are implicated in various neurological diseases such as epilepsy or autism.”

Specific Ions Prefer Specific Channel Structures

On their path to discovering how the non-selective NaK channel works, the scientists used a combination of nuclear magnetic resonance (NMR) spectroscopy and computer-assisted molecular dynamics simulations. The results revealed that the selectivity filter of the NaK channel dynamically changes between two structures. Each structure is conductive for one of the two ion types. Dr. Han Sun reports: “Surprisingly, the computer simulations showed that potassium ions passing through the NaK channel prefer the structure of a potassium selective channel, while the mechanism of the sodium ion passage is similar to the passage of sodium ions through a sodium selective ion channel.” Until now, researchers believed that the structure of the selectivity filter is the same for sodium and potassium ion transport through the NaK channel.

To gather further evidence for the crucial role of the dynamic structure of the NaK selectivity filter, the scientists experimented with a mutated NaK channel (NaK2K double point mutation). This mutated NaK channel is conductive only for potassium ions. Professor Adam Lange gives an account of the results: “Our NMR investigations clearly revealed that the selectivity filter of this channel forms only a single structure.”

Among other sources of financial support, the FMP scientists received funding from the DFG (Deutsche Forschungsgemeinschaft / German Research Foundation) as part of the funding for Research Group 2518 ‘Functional Dynamics of Ion Channels and Transporters’. The Norddeutscher Verbund für Hoch- und Hoechstleistungsrechnen (HLRN; Northern German Association for Supercomputing) in Berlin allowed the FMP scientists to use their computing power. Conducting the molecular dynamics simulations would have been impossible without this assistance.

Source:

http://www.leibniz-fmp.de/press-media/press-releases/press-releases-single-view1/article/a-matter-of-dynamics.html

Tagged with:

About author

Related Articles