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.
Gillespie
Dirk
D
Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, Illinois, USA. dirk_gillespie@rush.edu
Giri
Janhavi
J
Fill
Michael
M
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