Calculation of the conductance and selectivity of an ion-selective potassium channel (IRK1) from simulation of atomic scale models

We present the equations and methodology for the theoretical prediction of the conductance, permeability and selectivity of a K⁺ channel on the basis of atomic scale models for it. The methodology involves the use of Langevin dynamics and activated trajectories in order to obtain translocation free energies, rate constants and transmission coefficients for an ion going through the channel. The models are for the Inward Rectifier K⁺ channel (IRK1) which is a member of a family of ion-selective K⁺ channels. The IRK1 channel is biologically important because of its role in cardiac pacemaker function. The models we use for the IRK1 channel are developed from a model of the Shaker voltage-gated K⁺ channel. We find that the theoretically predicted conductance is too low by three orders of magnitude. We attribute this underestimate to a specific structural defect in the model used. Perhaps our most significant result is that the computed conductance is tremendously sensitive to the structural details of the so-called ‘P-loop’ that lines the outer half of the permeation pathway of the channel. This sensitivity may be useful in future studies on ion channel proteins for which the structure is not known from X-ray crystallography. In addition, this sensitivity may help determine whether X-ray structures of these proteins correspond to open or closed conformations.     

A Global Method for Relaxation in W1,p and in SBVp

 An integral representation formula for a class of functionals defined on and in (the space of special functions of bounded variation) is obtained without requiring the regularity conditions usually imposed in the literature. The approach is based on the general results of [10] and on a Poincaré-Wirtinger type inequality introduced by DE GIORGI, CARRIERO & LEACI [25]. Applications to relaxation problems and dimension-reduction problems in brittle thin films are presented. (Accepted May 8, 2002) Published online October 18, 2002 Communicated by L. Ambrosio     

THE PROTONATION OF A RETINYL SCHIFF BASE

The hydrogen bonding-protonation equilibrium for retinyl Schiff base/propionic acid or 3-chloropropionic acid systems was examined by Fourier transform infrared spectroscopy in non polar solutions at temperatures ranging from 25 degrees C to about -150 degrees C. The spectra give evidence for the gradual increase in the degree of protonation as temperature is lowered. The bearing of this on applying low temperature spectroscopic results to physiological conditions in rhodopsin research is discussed.     

Quantitative wideband spectroscopy with kilometric absorption paths

Combining Intra Cavity Laser Absorption and Time Resolved Fourier transform spectro-scopies (ICLAS-TRFTS) brings original advantages that are derived from the ability to obtain consistent series of Fourier spectra recorded according to a well-defined time sequence on the same accurate wavenumber scale. These advantages, mainly centred on the possibility to perform quantitative measurements are discussed and evaluated. Accurate determination of line positions and intensities of ultra weak transitions previously hardly measurable becomes possible. Ultimate limits are estimated for the present experiment in the neqr infrared range for H₂O.     

Newton's iteration for non-linear equations in Markov chains

A large number of queueing systems may be modelled as infiniteMarkov chains for which the transition matrix has a repetitivestructure. In order to determine the stationary distributionfor these Markov chains, it is necessary to find a particularsolution of a non-linear matrix equation. Various iterative algorithms have been proposed to determinethe matrix of interest. We consider here one particular algorithmand transform it by Newton's method. We show that Newton's algorithmis well defined and converges quadratically in the domain ofinterest.     

PHOTOCHEMICAL INTERACTIONS OF CHLORPROMAZINE WITH PHOSPHOLIPIDS AND CHOLESTEROL IN ARTIFICIAL AND NATURAL MEMBRANES

Abstract— Dipalmitoylphosphatidyl-choline (DPPC) liposomes do not modify the nature of the photoproducts formed by UV irradiation of chlorpromazine. However, when cholesterol is added to DPPC liposomes, new photoproducts are formed which demonstrate the photoaddition of chlorpromazine to cholesterol. Similar results are obtained with phosphatidyl-serine and phosphatidyl-inositol. The reactivity of irradiated chlorpromazine towards lipidic components of myelin, taken as an example of biological membrane, is also demonstrated.     

PHOTOCHEMICAL BINDING OF PHENOTHIAZINES ON BIOLOGICAL MEMBRANE PROTEINS

Abstract— The photobinding of phenothiazine derivatives (chlorpromazine, fluphenazine, promazine and promethazine) was studied on four different types of biological membranes (microsomes, myelin and synaptosomes from rat brain as well as human erythrocytes). The photoreaction was performed by ultraviolet irradiation of the tritiated compounds in their long wavelength absorption band (313 nm) and bound photoproducts were analysed by autoradiography of the proteins separated by polyacrylamide gel electrophoresis. The specificity of binding is low, however, a 34000 dalton band is intensely labeled on synaptic membranes with chlorpromazine and fluphenazine. All the phenothiazines bind on erythrocyte membrane proteins and specially on band 4.2 and on a peptide located before actin on the electrophoresis gel. These results show the generality of the phenothiazine photobinding on membrane proteins. These photobinding properties can be used for the identification and localization of some of these proteins.