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.
D000818:Animals; D001464:Barium / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D004594:Electrophysiology; D006168:Guinea Pigs; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
D018727:Muscarinic Antagonists; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D001464:Barium; D011188:Potassium