40,973 research outputs found
Thermodynamically Equivalent Silicon Models of Voltage-Dependent Ion Channels
We model ion channels in silicon by exploiting similarities between the thermodynamic principles that govern ion channels and those that govern transistors. Using just eight transistors, we replicate—for the first time in silicon—the sigmoidal voltage dependence of activation (or inactivation) and the bell-shaped voltage-dependence of its time constant. We derive equations describing the dynamics of our silicon analog and explore its flexibility by varying various parameters. In addition, we validate the design by implementing a channel with a single activation variable. The design’s compactness allows tens of thousands of copies to be built on a single chip, facilitating the study of biologically realistic models of neural computation at the network level in silicon
The influence of geometry, surface character and flexibility on the permeation of ions and water through biological pores
A hydrophobic constriction site can act as an efficient barrier to ion and
water permeation if its diameter is less than the diameter of an ion's first
hydration shell. This hydrophobic gating mechanism is thought to operate in a
number of ion channels, e.g. the nicotinic receptor, bacterial mechanosensitive
channels (MscL and MscS) and perhaps in some potassium channels (e.g. KcsA,
MthK, and KvAP). Simplified pore models allow one to investigate the primary
characteristics of a conduction pathway, namely its geometry (shape, pore
length, and radius), the chemical character of the pore wall surface, and its
local flexibility and surface roughness. Our extended (ca. 0.1 \mu s) molecular
dynamic simulations show that a short hydrophobic pore is closed to water for
radii smaller than 0.45 nm. By increasing the polarity of the pore wall (and
thus reducing its hydrophobicity) the transition radius can be decreased until
for hydrophilic pores liquid water is stable down to a radius comparable to a
water molecule's radius. Ions behave similarly but the transition from
conducting to non-conducting pores is even steeper and occurs at a radius of
0.65 nm for hydrophobic pores. The presence of water vapour in a constriction
zone indicates a barrier for ion permeation. A thermodynamic model can explain
the behaviour of water in nanopores in terms of the surface tensions, which
leads to a simple measure of "hydrophobicity" in this context. Furthermore,
increased local flexibility decreases the permeability of polar species. An
increase in temperature has the same effect, and we hypothesise that both
effects can be explained by a decrease in the effective solvent-surface
attraction which in turn leads to an increase in the solvent-wall surface free
energy.Comment: Peer reviewed article appeared in Physical Biology
http://www.iop.org/EJ/abstract/1478-3975/1/1/005
Ligand-dependent opening of the multiple AMPA receptor conductance states: a concerted model
Modulation of the properties of AMPA receptors at the post-synaptic membrane
is one of the main suggested mechanisms behind synaptic plasticity in the
central nervous system of vertebrates. Electrophysiological recordings of
single channels stimulated with agonists showed that both recombinant and
native AMPA receptors visit multiple conductance states in an agonist
concentration dependent manner. We propose an allosteric model of the multiple
conductance states based on concerted conformational transitions of the four
subunits, as an iris diaphragm. Our model predicts that the thermodynamic
behaviour of the conductance states upon full and partial agonist stimulations
can be described with increased affinity of receptors as they progress to
higher conductance states. The model also predicts existence of AMPA receptors
in non-liganded conductive substates. However, spontaneous openings probability
decreases with increasing conductances. Finally, we predict that the large
conductance states are stabilized within the rise phase of a whole-cell EPSC in
glutamatergic hippocampal neurons. Our model provides a mechanistic link
between ligand concentration and conductance states that can explain
thermodynamic and kinetic features of AMPA receptor gating.Comment: 4 figures, models available on demand. They will be published by
BioModels Database upon publication of the articl
Lipid Ion Channels
The interpretation electrical phenomena in biomembranes is usually based on
the assumption that the experimentally found discrete ion conduction events are
due to a particular class of proteins called ion channels while the lipid
membrane is considered being an inert electrical insulator. The particular
protein structure is thought to be related to ion specificity, specific
recognition of drugs by receptors and to macroscopic phenomena as nerve pulse
propagation. However, lipid membranes in their chain melting regime are known
to be highly permeable to ions, water and small molecules, and are therefore
not always inert. In voltage-clamp experiments one finds quantized conduction
events through protein-free membranes in their melting regime similar to or
even undistinguishable from those attributed to proteins. This constitutes a
conceptual problem for the interpretation of electrophysiological data obtained
from biological membrane preparations. Here, we review the experimental
evidence for lipid ion channels, their properties and the physical chemistry
underlying their creation. We introduce into the thermodynamic theory of
membrane fluctuations from which the lipid channels originate. Furthermore, we
demonstrate how the appearance of lipid channels can be influenced by the
alteration of the thermodynamic variables (temperature, pressure, tension,
chemical potentials) in a coherent description that is free of parameters. This
description leads to pores that display dwell times closely coupled to the
fluctuation lifetime via the fluctuation-dissipation theorem. Drugs as
anesthetics and neurotransmitters are shown to influence the channel likelihood
and their lifetimes in a predictable manner. We also discuss the role of
proteins in influencing the likelihood of lipid channel formation.Comment: Revie
- …