Quaternary ammonium ion blockade of IK in nerve axons revisited. Open channel block vs. state independent block.
The mechanism of blockade of the delayed rectifier potassium ion channel in squid giant axons by intracellular quaternary ammonium ions (QA) appears to be remarkably sensitive to the structure of the blocker. TEA, propyltriethyl-ammonium (C3), and propyltetraethylammonium (TAA-C3) all fail to alter the deactivation, or "tail" current time course following membrane depolarization, even with relatively large concentrations of the blockers, whereas butyltriethylammonium (C4), butyltetraethylammonium (TAA-C4), and pentytriethyammonium (C5) clearly do have such an effect. The relative electrical distance of blockade for all of these ions is approximately 0.25-0.3 from the inner surface of the membrane. The observations concerning TEA, C3, and TAA-C3 suggest that these ions can block the channel in either its open or its closed state. The results with C4, TAA-C4, and C5 are consistent with the open channel block model. Moreover, the sensitivity of block mechanism to the structure of the blocker suggests that the gate is located close to the QA ion binding site and that TEA, C3, and TAA-C3 do not interfere with channel gating, whereas C4, TAA-C4, C5, and ions having a longer hydrophobic "tail" than C5 do have such an effect. The parameters of block obtained for all QA ions investigated were unaffected by changes in the extracellular potassium ion concentration.
Clay
J R
JR
Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D001665:Binding Sites; D049832:Decapodiformes; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials; D008954:Models, Biological; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D026902:Potassium Channel Blockers; D000644:Quaternary Ammonium Compounds; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D011188:Potassium