Monte Carlo study of the selectivity of calcium channels: improved geometrical model

Boda, Dezső; Henderson, Douglas; Busath, David D.

doi:10.1080/00268970210125304

Cited by 46 publications

(78 citation statements)

References 24 publications

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“…The present calculations predict that channels with net charges of four or more would be multiply occupied, although not necessarily to electroneutrality. This is consistent with Monte Carlo [22,23,24,25] and molecular dynamics [19,20] simulations. In particular, with a model protein calcium channel, molecular dynamics simulations suggest [32] that when the channel is preloaded with two lateral calcium ions and one central sodium ion, one of the lateral Ca 2+ ions replaces the central Na + ion, typically forcing it out of the channel within 2 ns.…”

Section: Discussionsupporting

confidence: 87%

“…Models that exploit cylindrical geometry have already been used previously for Brownian dynamics simulations [13]. Several recent model studies have used a cylindrical geometry to represent the permeation pathway in calcium channels as well [17,18,19,20,21,22,23,24]. In all these studies the cylindrical pore has been charged by fixing specified discrete charges on the cylinder surface.…”

Section: Theory 21 Channel Modelmentioning

confidence: 99%

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Electrostatic control of occupancy and valence selectivity in a charged nanometer‐sized cylindrical pore

Spohr¹,

Sovyak

Trokhymchuk

et al. 2009

Materialwissenschaft Werkst

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Simple analytical calculations of the electrostatic energy for systems composed of positive charges confined to the axis of a negatively charged cylindrical pore are used to explore the role of electrostatic forces in the problems of ion permeation, ion occupancy and valence selectivity in biological ion channels. Considering the effect of finite length of the charged pore as an alternative to fixed charged residue representations, we show that ion occupancy and ion configurations in the pore are governed by two parameters: (i) the magnitude of the uniform surface charge density of the pore and (ii) the pore (diameter-to-length) aspect ratio through the interplay between favorable interaction of the mobile ions with the pore interior and unfavorable interaction among the ions themselves. The pore with an overall surface charge of -2e (representing a potassium channel) is found to favor occupancy by three K + ions over two K + ions at low aspect ratio but not at high. The pore with surface charge -4e (representing a calcium channel) favors occupancy by two lateral Ca 2+ ions and one central Na + ion over two symmetrically positioned Ca 2+ ions at a low aspect ratio, but this preference is reversed at a higher aspect ratio. These results allow us to speculate that Ca 2+ block of sodium current in the calcium channel is due to lower electrostatic energy for the Na + -Ca 2+ -Na + configuration than for the Na + -Na + -Na + configuration, and that the yet lower energy of the

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Section: Discussionsupporting

confidence: 87%

Section: Theory 21 Channel Modelmentioning

confidence: 99%

Electrostatic control of occupancy and valence selectivity in a charged nanometer‐sized cylindrical pore

Spohr¹,

Sovyak

Trokhymchuk

et al. 2009

Materialwissenschaft Werkst

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“…Other calcium channel models, at best, reproduce a very small amount of experimental data (30,38) and in many cases only consider ion binding in the selectivity filter, not current (29,(33)(34)(35)(36)38,(40)(41)(42). The RyR model also predicted (before experiments confirmed them) all of the known anomalous mole fraction effects of RyR (28,37) and how they change with voltage and concentrations (43).…”

Section: Introductionmentioning

confidence: 76%

“…Selectivity in this model is almost exclusively the result of electrostatics (30) and therefore it cannot distinguish between two ion species of the same valence (31,32). The model pore of Nonner et al (29), however, predicts large differences in affinity between monovalent cations (28,29,(33)(34)(35)(36)(37).…”

Section: Introductionmentioning

confidence: 88%

“…The carboxyls in the pore make a highly charged environment that attracts cations, while at the same time making a very crowded, liquid-like environment where ions must compete for space with each other and the carboxyls. In this charge/space competition (CSC) mechanism, selectivity is a balance of electrostatic and excluded-volume forces (i.e., two ions cannot overlap) (28,29,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42).…”

Section: Introductionmentioning

confidence: 99%

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Selecting Ions by Size in a Calcium Channel: The Ryanodine Receptor Case Study

Gillespie

Meissner

2014

Biophysical Journal

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Many calcium channels can distinguish between ions of the same charge but different size. For example, when cations are in direct competition with each other, the ryanodine receptor (RyR) calcium channel preferentially conducts smaller cations such as Li(+) and Na(+) over larger ones such as K(+) and Cs(+). Here, we analyze the physical basis for this preference using a previously established model of RyR permeation and selectivity. Like other calcium channels, RyR has four aspartate residues in its GGGIGDE selectivity filter. These aspartates have their terminal carboxyl group in the pore lumen, which take up much of the available space for permeating ions. We find that small ions are preferred by RyR because they can fit into this crowded environment more easily.

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Crowded Charges in Ion Channels

Eisenberg

2011

Advances in Chemical Physics

129

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Physical Chemistry and Life. Ions in water are the liquid of life. Life occurs almost entirely in 'salt water'. Life began in salty oceans. Animals kept that salt water within them when they moved out of the ocean to drier surroundings. The plasma and blood that surrounds all cells are electrolytes more or less resembling sea water. The plasma inside cells is an electrolyte solution that more or less resembles the sea water in which life began. Water itself (without ions) is lethal to animal cells and damaging for most proteins. Water must contain the right ions in the right amounts if it is to sustain life.Physical chemistry is the language of electrolyte solutions and so physical chemistry, and biology, particularly physiology, have been intertwined since physical chemistry was developed some one hundred fifty years ago. Physiology, of course, was studied by the Greeks some millennia earlier, but the biological role of electrolyte solutions could not be understood until ions were discovered by chemists some 2,000 years later.Physical chemists and biologists come from different traditions that separated for several decades as biologists identified and described the molecules of life. Communication is not easy between a fundamentally descriptive tradition and a fundamentally analytical one. Biologists have now learned to study their well defined systems with physical techniques, of considerable interest to physical chemists. Physical chemists are increasingly interested in spatially inhomogeneous systems with structures on the atomic scale so common in biology. Physical chemists will find it productive to work on well defined systems built by evolution to be reasonably robust, with input output relations insensitive to environmental insults. The overlap in science is clear. The human overlap is harder because the fields have grown independently for some time, and the knowledge base, assumptions, and jargon of the fields do not coincide. Indeed, they sometimes seem disjoint, without overlap.This article deals with properties of ion channels that in my view can be dealt with by 'physics as usual', with much the same tools that physical chemists apply to other systems. Indeed, I introduce and use a tool of physicists-a field theory (and boundary conditions) based on an energy variational approach developed by Chun Liu 141,575,766,806,944 -not too widely used among physical chemists. My goal is to provide the knowledge base, and identify the assumptions, that biologists use in studying ion channels, avoiding jargon. Although we do not know enough to write atomic, detailed physical models of the process by which ions move through channels, rather simple models of selectivity and permeation work quite well in important cases. Those physical models and cases are the main focus of this review because they demonstrate the strong essential link between the traditional treatments of ions in chemical physics, and the biological function of ion channels.At first, ion channels may seem to be an extreme system. They are as smal...

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Monte Carlo study of the selectivity of calcium channels: improved geometrical model

Cited by 46 publications

References 24 publications

Electrostatic control of occupancy and valence selectivity in a charged nanometer‐sized cylindrical pore

Electrostatic control of occupancy and valence selectivity in a charged nanometer‐sized cylindrical pore

Selecting Ions by Size in a Calcium Channel: The Ryanodine Receptor Case Study

Crowded Charges in Ion Channels

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