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

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

Enlargement of the third ventricle and hyponatraemia in aneurysmal subarachnoid haemorrhage.

Hyponatraemia following aneurysmal subarachnoid haemorrhage is associated with an increased risk of cerebral infarction. Whether the development of hyponatraemia was related to enlargement of the third ventricle on the admission CT scan was investigated in a consecutive series of 133 patients who were seen within 72 hours of aneurysmal haemorrhage. Hyponatraemia occurred significantly more often in patients with enlargement of the third ventricle (with or without dilatation of the lateral ventricles) than in patients with a normal ventricular system (20/41 versus 24/92, p = 0.016). After ventricular drainage, the sodium levels returned to normal in two patients in whom the size of the third ventricle decreased and not in four patients with persistent enlargement of the third ventricle. The significant relationship between enlargement of the third ventricle and hyponatraemia remained after adjustment for the amount of cisternal blood, but not after adjustment for the amount of intraventricular blood. These results suggest that the size of the third ventricle is an important but not the only factor in the relationship between acute hydrocephalus and hyponatraemia in patients with aneurysmal subarachnoid haemorrhage

A Radial Basis Function Spike Model for Indirect Learning via Integrate-and-Fire Sampling and Reconstruction Techniques

This paper presents a deterministic and adaptive spike model derived from radial basis functions and a leaky integrate-and-fire sampler developed for training spiking neural networks without direct weight manipulation. Several algorithms have been proposed for training spiking neural networks through biologically-plausible learning mechanisms, such as spike-timing-dependent synaptic plasticity and Hebbian plasticity. These algorithms typically rely on the ability to update the synaptic strengths, or weights, directly, through a weight update rule in which the weight increment can be decided and implemented based on the training equations. However, in several potential applications of adaptive spiking neural networks, including neuroprosthetic devices and CMOS/memristor nanoscale neuromorphic chips, the weights cannot be manipulated directly and, instead, tend to change over time by virtue of the pre- and postsynaptic neural activity. This paper presents an indirect learning method that induces changes in the synaptic weights by modulating spike-timing-dependent plasticity by means of controlled input spike trains. In place of the weights, the algorithm manipulates the input spike trains used to stimulate the input neurons by determining a sequence of spike timings that minimize a desired objective function and, indirectly, induce the desired synaptic plasticity in the network