Reinterpreting the anomalous mole fraction effect: the ryanodine receptor case study.
The origin of the anomalous mole fraction effect (AMFE) in calcium channels is explored with a model of the ryanodine receptor. This model predicted and experiments verified new AMFEs in the cardiac isoform. In mole fraction experiments, conductance is measured in mixtures of ion species X and Y as their relative amounts (mole fractions) vary. This curve can have a minimum (an AMFE). The traditional interpretation of the AMFE is that multiple interacting ions move through the pore in a single file. Mole fraction curves without minima (no AMFEs) are generally interpreted as X displacing Y from the pore in a proportion larger than its bath mole fraction (preferential selectivity). We find that the AMFE is also caused by preferential selectivity of X over Y, if X and Y have similar conductances. This is a prediction applicable to any channel and provides a fundamentally different explanation of the AMFE that does not require single filing or multiple occupancy: preferential selectivity causes the resistances to current flow in the baths, channel vestibules, and selectivity filter to change differently with mole fraction, and produce the AMFE.
Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, Illinois, USA. dirk_gillespie@rush.edu
Dirk
D
Gillespie
Janhavi
J
Giri
Michael
M
Fill
D000465:Algorithms; D000818:Animals; D002118:Calcium / Q000737:chemistry; D002586:Cesium / Q000737:chemistry; D007700:Kinetics; D008094:Lithium / Q000737:chemistry; D008564:Membrane Potentials; D008954:Models, Biological; D011188:Potassium / Q000737:chemistry; D020033:Protein Isoforms / Q000737:chemistry; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry*; D012964:Sodium / Q000378:metabolism
D020033:Protein Isoforms; D019837:Ryanodine Receptor Calcium Release Channel; D002586:Cesium; D008094:Lithium; D012964:Sodium; D011188:Potassium; D002118:Calcium