Conductance selectivity of Na+ across the K+ channel via Na+ trapped in a tortuous trajectory

Ion selectivity of the potassium channel is crucial for regulating electrical activity in living cells; however, the mechanism underlying the potassium channel selectivity that favors large K+ over small Na+ remains unclear. Generally, Na+ is not completely excluded from permeation through potassium channels. Herein, the distinct nature of Na+ conduction through the prototypical KcsA potassium channel was examined. Single-channel current recordings revealed that, at a high Na+ concentration (200 mM), the channel was blocked by Na+, and this blocking was relieved at high membrane potentials, suggesting the passage of Na+ across the channel. At a 2,000 mM Na+ concentration, single-channel Na+ conductance was measured as one-eightieth of the K+ conductance, indicating that the selectivity filter allows substantial conduit of Na+. Molecular dynamics simulations revealed unprecedented atomic trajectories of Na+ permeation. In the selectivity filter having a series of carbonyl oxygen rings, a smaller Na+ was distributed off-center in eight carbonyl oxygen-coordinated sites as well as on-center in four carbonyl oxygen-coordinated sites. This amphipathic nature of Na+ coordination yielded a continuous but tortuous path along the filter. Trapping of Na+ in many deep free energy wells in the filter caused slow elution. Conversely, K+ is conducted via a straight path, and as the number of occupied K+ ions increased to three, the concerted conduction was accelerated dramatically, generating the conductance selectivity ratio of up to 80. The selectivity filter allows accommodation of different ion species, but the ion coordination and interactions between ions render contrast conduction rates, constituting the potassium channel conductance selectivity.

Lipid distributions and transleaflet cholesterol migration near heterogeneous surfaces in asymmetric bilayers

Specific and nonspecific protein-lipid interactions in cell membranes have important roles in an abundance of biological functions. We have used coarse-grained (CG) molecular dynamics (MD) simulations to assess lipid distributions and cholesterol flipping dynamics around surfaces in a model asymmetric plasma membrane containing one of six structurally distinct entities: aquaporin-1 (AQP1), the bacterial β-barrel outer membrane proteins OmpF and OmpX, KcsA potassium channel, WALP23 peptide, and a carbon nanotube (CNT). Our findings revealed varied lipid partitioning and cholesterol flipping times around the different solutes, and putative cholesterol binding sites in AQP1 and KcsA. The results suggest that protein-lipid interactions can be highly variable, and that surface-dependant lipid profiles are effectively manifested in CG simulations with the Martini force field.

Proceedings - CBIOS Science Sessions 2020

Science Sessions 2020 Catarina Rosado and L Monteiro Rodrigues, eds. Vinicius Cuña, Universidade Lusófona de Humanidades e Tecnologias `````````````````````````````````` p.2 Oxygen Ozone Therapy - Tool in Veterinary Medicine Oxigênio Ozônio Terapia - Ferramenta na Medicina Veterinária Elisabete Silva, Faculdade de Ciências da Universidade de Lisboa p.2 Eco-friendly mon-biocide-releasing antifouling coatings for biofouling prevention Revestimentos antivegetativos monocidas amigos do ambiente para a prevenção de biofouling Amélia Pilar Rauter, Centro de Química Estrutural, Faculdade de Ciências; Universidade de Lisboa, p.3 Departamento de Química e Bioquímica, CiênciasULisboa. The sustainable chemistry of sugars: New antibacterial with a new mechanism of action A química sustentável dos açúcares: Novos antibacterianos com um novo mecanismo de ação Sofia Ramos, CBIOS Lusófona’s Research Center for Biosciences and Health Technologies p.4 Expression profile of cellular redox and calcium signaling-related genes: role in breast cancer progression Perfil de expressão de genes redox celulares e de sinalização de cálcio: papel na progressão do cancro da mama Ana Coutinho, Departamento de Química e Bioquímica. Faculdade de Ciências da Universidade de Lisboa p.4 Studying the conformational plasticity of KcsA potassium channel by homo-FRET Estudo da plasticidade conformacional do canal de potássio KcsA por homo-FRET Andreia Valente, Centro de Química Estrutural da Faculdade de Ciências da Universidade de Lisboa` p.5 Targeted cancer therapy using ruthenium compounds Terapia específica do cancro usando compostos de ruténio Sérgio Faloni Andrade, CBIOS Lusófona’s Research Center for Biosciences and Health Technologies p.5 Natural products and their potential to treat gastrointestinal inflammatory and ulcerative diseases Produtos naturais e o seu potencial para tratar doenças inflamatórias e ulcerativas gastrointestinais Cláudia Nunes, LAQV, Requimte, FFUP p.6 Fat nanoparticles: a diet towards targeted nano delivery Nanopartículas de gordura: uma dieta orientada para a nanodeficiência Cíntia Ferreira-Pêgo, CBIOS Lusófona’s Research Center for Biosciences and Health Technologies p.6 Mediterranean diet adherence, eating behavior and body shape concerns in Portuguese university students Adesão à dieta mediterrânica, comportamento alimentar e preocupações com a forma do corpo em estudantes universitários portugueses João Gregório, CBIOS Lusófona's Research Center for Biosciences and Health Technologies p. 7 "Pharmacists' guide to the future: challenges and opportunities for research and development of pharmacy services" "Guia dos farmacêuticos para o futuro: desafios e oportunidades para a investigação e desenvolvimento dos serviços de farmácia" Andreia Valença, Universidade Lusófona de Humanidades e Tecnologias p. 7 TIM2: a new membrane receiver for ferritin-H in the retina of murganho TIM2: um novo receptor de membrana para a ferritina-H na retina de murganho

Cracking the Secret Code of the Selectivity Ratio Between K+ and Na+ Ions in the KcsA K+ Channel

The KcsA is a prokaryotic potassium-oriented channel, which is sourced from the Streptomyces lividans soil bacteria. From extensive studies that have been carried over the KcsA potassium channel, it has been proved that various factors enable the gating and shuttling of the potassium ions into and out of the cells. Some of the factors include the different concentration of protons in the inside and outside membrane. The other factor is the existence of the selectivity filter equipped in the exit of channel pore, which enables the movement of the K+ ions. Not only are potassium ions present in the channel but also sodium ions. Potassium and sodium ions are the ions that are essential in the conductivity of a cell because of their charge. An intuitive idea about why K+ ions are at least 10,000 times more permeant than Na+ ions is presented in various entities. The hypothesis is that the selectivity ratio is probably related to the successive entry of Na+ ions, based on the premise that the ratio seems to be relevant to unpredictable quantities caused by Brownian corrosion of ions.

Cracking the Secret Code of the Selectivity Ratio Between K+ and Na+ Ions in the KcsA K+ Channel

The KcsA is a prokaryotic potassium-oriented channel, which is sourced from the Streptomyces lividans soil bacteria. From extensive studies that have been carried over the KcsA potassium channel, it has been proved that various factors enable the gating and shuttling of the potassium ions into and out of the cells. Some of the factors include the different concentration of protons in the inside and outside membrane. The other factor is the existence of the selectivity filter equipped in the exit of channel pore, which enables the movement of the K+ ions. Not only are potassium ions present in the channel but also sodium ions. Potassium and sodium ions are the ions that are essential in the conductivity of a cell because of their charge. An intuitive idea about why K+ ions are at least 10,000 times more permeant than Na+ ions is presented in various entities. The hypothesis is that the selectivity ratio is probably related to the successive entry of Na+ ions, based on the premise that the ratio seems to be relevant to unpredictable quantities caused by Brownian corrosion of ions.