Sarcoplasmic Reticulum K+ Channels from Human and Sheep Atrial Cells Display a Specific Electro-pharmacological Profile

L. Picard, K. Côté, J. Teijeira, D. Greentree and E. Rousseau. Sarcoplasmic Reticulum K+ Channels from Human and Sheep Atrial Cells Display a Specific Electro-pharmacological Profile. Journal of Molecular and Cellular Cardiology (2002) 34, 1163–1172. It has recently been proposed that the Ca2+ uptake by the SR is inhibited by blocking Cl− and/or K+ movements across this intracellular membrane. We have characterised the functional and pharmacological profile of the SR K+ channel derived from human and sheep atrial cells. Mammalian atrial SR preparations were subjected to [3H]-ryanodine binding assays, SDS-PAGE analysis and channel protein reconstitution into planar lipid bilayers. Assessment of [3H]-ryanodine binding on the SR Ca2+ release channel revealed that it was inhibited by both Ruthenium Red and Mg2+ with IC50 values of 4.11 μimage and 9.12 m image, respectively. In crude populations as well as in all SR-enriched fractions, activity of K+ selective channels was recorded. This channel displayed a high conductance value of 193 and 185 pS for human and sheep preparations respectively. Gating and conducting behaviours of this channel were unaffected by the addition of up to 5 m M 4-Aminopyridine (4-AP), 100 n M Iberiotoxin (IbTX), 10 μM E-4031 and 30 μM amiodarone. However, 100 n M Dendrotoxin (γ-DTX) largely increase the occurrence of the SR K+ channel subconducting states without an effect on the main unitary conductance. These results demonstrate that the SR K+ channel, present in all mammalian atrial SR membranes tested (as assessed by [3H]-ryanodine binding and its typical inhibition by ruthenium red and the magnesium), displays different properties than those classically described for cardiac sarcolemmal K+ channels. Despite the fact that the biophysical properties of the SR K+ channel are well known, its molecular identity remains to be ascertained.