Barium block of the muscarinic potassium current in guinea-pig atrial cells.

Block of the muscarinic K+ current (iK,ACh) by Ba2+ has been studied in guinea-pig atrial cells using the whole-cell patch-clamp technique. The dose-response curve for the block of iK,ACh can be fitted assuming that a muscarinic K+ channel is blocked when a single Ba2+ ion binds to it (apparent dissociation constant, Kd = 125 microM at 0 mV). Block was voltage and time dependent. The voltage dependence can be explained by Ba2+ binding to a site within the pore of the channel, 36% across the width of the membrane electric field (from the outside). Raising the bathing K+ concentration reduced Ba2+ block of iK,ACh, which suggests that Ba2+ and K+ compete for a common binding site. When Ba2+ was added during an exposure to ACh (muscarinic K+ channel open), block of iK,ACh developed rapidly, but when Ba2+ was added prior to an exposure to ACh (muscarinic K+ channel closed), little block of iK,ACh was evident when ACh was first applied. This suggests that when the muscarinic K+ channel is closed in the absence of ACh, Ba2+ does not have access to the binding site within the pore of the channel. In conclusion, Ba2+ block of iK,ACh is concentration, voltage, time, K+ and state dependent.