Monovalent cation conductance in the ryanodine receptor‐channel of sheep cardiac muscle sarcoplasmic reticulum.

Abstract

SUMMARY1. The ryanodine receptor protein of sheep cardiac muscle sarcoplasmic reticulum membranes functions as a ligand-regulated ion channel following solubilization with the zwitterionic detergent CHAPS (3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulphonate); purification by density gradient centrifugation, reconstitution into proteo-liposomes and incorporation into planar phospholipid bilayers.2. In the absence of divalent cations, measurable conductance is observed with the group la cations and with some larger organic cations. In symmetric 210 mM solutions the following conductance sequence was determined: K+ > Rb+ NH4+ > Na+ = Cs+ > Li+ > Tris+.3. Other organic cations, e.g. TEA+, do not produce measurable current under these conditions. 4. Single-channel conductance saturates with increasing ionic activities of K+, Na+ and Li+. Saturation curves are described by Michaelis-Menten kinetic schemes with the following values of maximal conductance and apparent dissociation constant: K+ 900 pS, 19-9 mM; Na+ 516 pS, 17-8 mM; Li' 248 pS, 9-1 mM.5. The channel displays only minor differences in permeability amongst the group la cations. Relative permeability, monitored under bi-ionic conditions, yields the following sequence: Na+, 1-15 > K+, 1-00 = Li+, 0 99 > Rb+, 0-87 > Cs+, 0-61. Under similar conditions the permeability ratio of NH4+ to K+ was found to be 1-32 and that for Tris+ to K+ was 0-22.6. The K+ conductance is reduced by low concentrations of the impermeant cation TEA+. Block appears as a smooth reduction in single-channel current amplitude and the degree of block is dependent upon applied voltage. These observations are consistent with a single-site blocking scheme in which TEA+ has access to a site within the voltage drop of the channel from only the cytosolic face of the channel protein and interacts with a site located approximately 90% of the electrical distance across the channel. The zero-voltage dissociation constant for TEA+ block is 50 mM.7. Single-channel conductance measurements in mixtures of K+-Na+ and K+-Li+ reveal no anomalous behaviour as the mole fraction of the ions is varied.8

Organic Cation Permeation through the Channel Formed by Polycystin-2

“…2A). This observation is similar to that seen when organic amines of varying sizes conduct through the intracellular calcium channel, the RyR (11,13,19).…”

Putative ryanodine receptors in the sarcolemma of ventricular myocytes

“…The RyR has complex biophysical and pharmacological properties. Both monovalent and divalent cations permeate the channel with a large single-channel conductance (for monovalent ions 400-700 pS; for divalent ions: 80-180 pS) [10,22] and multiple subconductance states. Agents such as Ca 2+ , Mg 2+ , adenosine 5′-triphosphate (ATP), caffeine, ryanodine, ruthenium red and others modulate its activity [14], as do associated membrane proteins.…”

Inositol Trisphosphate Receptor Ca2+Release Channels

“…More likely, it is caused by the use of Cs ϩ rather than K ϩ as the permeant ion. Although the relative conductances of Cs ϩ and K ϩ in the InsP 3 R have not been determined, Cs ϩ currents through RyR channels are only 60% as large as those carried by K ϩ (255). Given the strong structural and functional similarities of the pore properties of InsP 3 R and RyR (discussed earlier and in additional detail below), it is possible that Cs ϩ currents are smaller in InsP 3 R channels as well, and that the type 2 channel K ϩ conductance is therefore similar to that of the other isoforms.…”