A model is developed for ionic conduction in the sheep cardiac sarcoplasmic reticulum ryanodine receptor channel based on Eyring rate theory. A simple scheme is proposed founded on single-ion occupancy and an energy profile with four barriers and three binding sites. The model is able to quantitatively predict a large number of conduction properties of the purified and native receptor with monovalent and divalent cations as permeant species. It suggests that discrimination between divalent and monovalent cations is due to a high affinity central binding site and a process that favors the passage of divalent cations between binding sites. Furthermore, differences in conductance among the group Ia cations and among the alkaline earths are largely explained by differing affinity at this putative central binding site.

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