The anomalous mole fraction effect in calcium channels: a measure of preferential selectivity.
The cause of the anomalous mole fraction effect (AMFE) in calcium-selective ion channels is studied. An AMFE occurs when the conductance through a channel is lower in a mixture of salts than in the pure salts at the same concentration. The textbook interpretation of the AMFE is that multiple ions move through the pore in coordinated, single-file motion. Instead of this, we find that at its most basic level an AMFE reflects a channel's preferential binding selectivity for one ion species over another. The AMFE is explained by considering the charged and uncharged regions of the pore as electrical resistors in series: the AMFE is produced by these regions of high and low ion concentration changing differently with mole fraction due to the preferential ion selectivity. This is demonstrated with simulations of a model L-type calcium channel and a mathematical analysis of a simplistic point-charge model. The particle simulations reproduce the experimental data of two L-type channel AMFEs. Conditions under which an AMFE may be found experimentally are discussed. The resistors-in-series model provides a fundamentally different explanation of the AMFE than the traditional theory and does not require single filing, multiple occupancy, or momentum-correlated ion motion.
Gillespie
Dirk
D
Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, Illinois, USA. dirk_gillespie@rush.edu
Boda
Dezso
D
D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D004553:Electric Conductivity; D008954:Models, Biological; D009010:Monte Carlo Method; D016062:Porosity; D012964:Sodium / Q000378:metabolism; D055672:Static Electricity; D013379:Substrate Specificity
D015220:Calcium Channels; D001464:Barium; D012964:Sodium; D002118:Calcium