Monte Carlo study of gating and selection in potassium channels

The study of selection and gating in potassium channels is a very important issue in modern biology. Indeed such structures are known in all types of cells in all organisms where they play many important functional roles. The mechanism of gating and selection of ionic species is not clearly understood. In this paper we study a model in which gating is obtained via an affinity-switching selectivity filter. We discuss the dependence of selectivity and efficiency on the cytosolic ionic concentration and on the typical pore open state duration. We demonstrate that a simple modification of the way in which the selectivity filter is modeled yields larger channel efficiency

Emergent bursting and synchrony in computer simulations of neuronal cultures

Experimental studies of neuronal cultures have revealed a wide variety of spiking network activity ranging from sparse, asynchronous firing to distinct, network-wide synchronous bursting. However, the functional mechanisms driving these observed firing patterns are not well understood. In this work, we develop an in silico network of cortical neurons based on known features of similar in vitro networks. The activity from these simulations is found to closely mimic experimental data. Furthermore, the strength or degree of network bursting is found to depend on a few parameters: the density of the culture, the type of synaptic connections, and the ratio of excitatory to inhibitory connections. Network bursting gradually becomes more prominent as either the density, the fraction of long range connections, or the fraction of excitatory neurons is increased. Interestingly, biologically prevalent values of parameters result in networks that are at the transition between strong bursting and sparse firing. Using principal components analysis, we show that a large fraction of the variance in firing rates is captured by the first component for bursting networks. These results have implications for understanding how information is encoded at the population level as well as for why certain network parameters are ubiquitous in cortical tissue

Cooperative Transition between Open and Closed Conformations in Potassium Channels

Potassium (K+) ion channels switch between open and closed conformations. The nature of this important transition was revealed by comparing the X-ray crystal structures of the MthK channel from Methanobacterium thermoautotrophicum, obtained in its open conformation, and the KcsA channel from Streptomyces lividans, obtained in its closed conformation. We analyzed the dynamic characteristics and energetics of these homotetrameric structures in order to study the role of the intersubunit cooperativity in this transition. For this, elastic models and in silico alanine-scanning mutagenesis were used, respectively. Reassuringly, the calculations manifested motion from the open (closed) towards the closed (open) conformation. The calculations also revealed a network of dynamically and energetically coupled residues. Interestingly, the network suggests coupling between the selectivity filter and the gate, which are located at the two ends of the channel pore. Coupling between these two regions was not observed in calculations that were conducted with the monomer, which emphasizes the importance of the intersubunit interactions within the tetrameric structure for the cooperative gating behavior of the channel

For whom and under what circumstances do school-based energy balance behavior interventions work? Systematic review on moderators

The aim of this review was to systematically review the results and quality of studies investigating the moderators of school-based interventions aimed at energy balance-related behaviors. We systematically searched the electronic databases of Pubmed, EMBASE, Cochrane, PsycInfo, ERIC and Sportdiscus. In total 61 articles were included. Gender, ethnicity, age, baseline values of outcomes, initial weight status and socioeconomic status were the most frequently studied potential moderators. The moderator with the most convincing evidence was gender. School-based interventions appear to work better for girls than for boys. Due to the inconsistent results, many studies reporting non-significant moderating effects, and the moderate methodological quality of most studies, no further consistent results were found. Consequently, there is lack of insight into what interventions work for whom. Future studies should apply stronger methodology to test moderating effects of important potential target group segmentations

Activation-Dependent Subconductance Levels in the drk1 K Channel Suggest a Subunit Basis for Ion Permeation and Gating

Ion permeation and channel opening are two fundamental properties of ion channels, the molecular bases of which are poorly understood. Channels can exist in two permeability states, open and closed. The relative amount of time a channel spends in the open conformation depends on the state of activation. In voltage-gated ion channels, activation involves movement of a charged voltage sensor, which is required for channel opening. Single-channel recordings of drk1 K channels expressed in Xenopus oocytes suggested that intermediate current levels (sublevels) may be associated with transitions between the closed and open states. Because K channels are formed by four identical subunits, each contributing to the lining of the pore, it was hypothesized that these sublevels resulted from heteromeric pore conformations. A formal model based on this hypothesis predicted that sublevels should be more frequently observed in partially activated channels, in which some but not all subunits have undergone voltage-dependent conformational changes required for channel opening. Experiments using the drk1 K channel, as well as drk1 channels with mutations in the pore and in the voltage sensor, showed that the probability of visiting a sublevel correlated with voltage- and time-dependent changes in activation. A subunit basis is proposed for channel opening and permeation in which these processes are coupled

Classification of musical styles using liquid state machines

10.1109/IJCNN.2010.5596470Proceedings of the International Joint Conference on Neural Networks-85OF