Permeation of Ions Through Membrane Channels
Department of Chemistry, The Faculties
Toby W. Allen
Department of Chemistry,The Faculties
Department of Theoretical Physics
Research School of Physical Sciences & Engineering
r06 - VPP
Measurement of ionic currents flowing through
Despite the wealth of information accumulated over the past decade, how ion channels work is not well understood. The mechanisms of ion channels that need to be explained are those of conductance, selectivity, and gating: their ability to rapidly pass large numbers of ions, their ability to pass some types of ions while blocking others, and their ability to open in response to electrical or chemical signals, and close a short time later. These are some of the basic questions our research addresses. Our approach is, first, to develop theoretical models that can relate the structural parameters of channels to experimental measurements and then to test the validity of these models using the technique of computer simulation
What are the results to date and the future work?
Recently, one important type of biological ion channel, namely, the potassium channel from soil bacterium, has been crystallized and its crystallographic structure was deduced by a group in America. Incorporating this newly unveiled structural information into our Brownian dynamics algorithm, we have examined several key issues on the permeation of ions across this channel. The results of simulations are in agreement with several experimental observations on this channel. Among these are: the channel conductance, conductance-concentration curve, current-voltage relationships and the reversal potential in asymmetrical ionic solutions.
- Appendix A
We are now planning to explore, firstly, how this channel becomes permeable to K+ but not to Na+. The channel is also impermeable to Li+ and has a selectivity sequence of Tl+ > K+ > Rb+ > NH4+. We wish to unravel the mechanisms that give rise to this selectivity sequence. There are many other types of potassium channels, and they differ in their single-channel conductance but show strong similarities in their permeability mechanism. We are planning to investigate what structural features must be modified to yield the observed biophysical properties of other types of potassium channels.
What computational techniques are used?
Our Brownian dynamics program uses the algorithm devised by van Gunsteren and Berendsen. We use reflective boundaries to prevent ions from penetrating the walls of the channel or escaping from the reservoirs at either end. To reduce the amount of computational effort involved in simulating a system of charged particles interacting with the protein wall, we precalculate the values of the electric field by solving Poisson's equation numerically for a grid of positions and then store them in a set of lookup tables. Using a multidimensional interpolation algorithm, the field and potential experienced by an ion at any position can be deduced from the information stored in the lookup tables. With the speed gained with this method, we are able to run the computer simulations long enough to determine the conductance of the channel.
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Appendix A -