A model for ionic conduction in the ryanodine receptor channel of sheep cardiac muscle sarcoplasmic reticulum.

Abstract

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 sin#e-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.

Glutathione S‐transferase gene polymorphism and cardiac iron overload in thalassaemia major

“…This could be due to the difference in permeability among the divalent cations of these channels, as already demonstrated for Ba 2+ , Sr 2+ and Mg 2+ (Tinker et al, 1992). This hypothesis is also supported by the finding that L-type Ca 2+ channels are high-capacity pathways of ferrous iron uptake into cardiomyocytes under iron overload conditions (Oudit et al, 2006).…”

Inositol Trisphosphate Receptor Ca2+Release Channels

“…The effect of Mg 2ϩ could not be accounted for by electrostatic screening by Mg 2ϩ of surface charges around the channel pore or competitive block of the channel pore by impermeant Mg 2ϩ present on one side of the channel (276). The effects of Mg 2ϩ are reminiscent of the effects of divalent cations on the monovalent cation conductance of the RyR (471,472). The RyR has a high Mg 2ϩ permeability (473), similar to the InsP 3 R. There, it has been proposed that divalent cations experience low energy barriers to entry into the pore of the RyR, which enables them to move into the conduction pathway with relatively high permeabilities compared with monovalent cations (471,472).…”

“…The effects of Mg 2ϩ are reminiscent of the effects of divalent cations on the monovalent cation conductance of the RyR (471,472). The RyR has a high Mg 2ϩ permeability (473), similar to the InsP 3 R. There, it has been proposed that divalent cations experience low energy barriers to entry into the pore of the RyR, which enables them to move into the conduction pathway with relatively high permeabilities compared with monovalent cations (471,472). However, since the divalent ions bind tightly in a potential well inside the channel pore, they therefore permeate through the channel pore more slowly than monovalent ions.…”

“…High applied voltages alleviate the block by increasing the rate at which divalent ions move through the channel, thus generating nonlinearity in the I-V relation. The conversion of the linear monovalent cation I-V relation in the absence of divalent cations to the rectified I-V relations in their presence (both Mg 2ϩ and Ba 2ϩ ) observed in both the InsP 3 R and RyR (276,471,472) strongly suggests that this model for ionic conduction is applicable to the InsP 3 R. These results indicate that the InsP 3 R has a pore which possesses lower energy barriers for divalent (Ca 2ϩ and Mg 2ϩ ) relative to monovalent (K ϩ ) cation entry, and therefore higher divalent cation permeabilities, and relatively stronger divalent cation binding sites, which cause divalent ion blocking of the channel (276). Mg 2ϩ inhibited K ϩ conductance of the InsP 3 R with an apparent dissociation constant of 560 M (276), indicating that the divalent binding site has high affinity that enables it to bind divalent cations at physiologically important concentrations.…”

Calcium inactivation of calcium release in frog cut muscle fibers that contain millimolar EGTA or Fura-2.

“…and Tinker, Lindsay, and Williams (1992) have carfled out an extensive analysis of the permeability properties of purified ryanodine receptor channels isolated from sheep cardiac muscle. From their results, Tinker, Lindsay, and Williams (1993) estimate a value of 2 pA for the single-channel current at 0 mV and 21~ with 2.5 mM Ca on the luminal side of the membrane only.…”