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Science 2 February 1996:
Vol. 271. no. 5249, pp. 653 - 656
DOI: 10.1126/science.271.5249.653
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Reports

Use-Dependent Blockers and Exit Rate of the Last Ion from the Multi-Ion Pore of a K+ Channel

Thomas Baukrowitz and Gary Yellen (1)

Quaternary ammonium blockers inhibit many voltage-activated potassium (K+) channels from the intracellular side. When applied to Drosophila Shaker potassium channels expressed in mammalian cells, these rapidly reversible blockers produced use-dependent inhibition through an unusual mechanism-they promoted an intrinsic conformational change known as C-type inactivation, from which recovery is slow. The blockers did so by cutting off potassium ion flow to a site in the pore, which then emptied at a rate of 105 ions per second. This slow rate probably reflected the departure of the last ion from the multi-ion pore: Permeation of ions (at 107 per second) occurs rapidly because of ion-ion repulsion, but the last ion to leave would experience no such repulsion.


Department of Neurobiology, Harvard Medical School and Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114, USA.
(1) To whom correspondence should be addressed.


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E. M. Ogielska and R. W. Aldrich (1999)
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Mechanistic link between lidocaine block and inactivation probed by outer pore mutations in the rat {micro}1 skeletal muscle sodium channel.
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Activity-Dependent Modulation of Glutamate Receptors by Polyamines.
D. Bowie, G. D. Lange, and M. L. Mayer (1998)
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Protein Rearrangements Underlying Slow Inactivation of the Shaker K+ Channel.
E. Loots and E.Y. Isacoff (1998)
J. Gen. Physiol. 112, 377-389
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Coupled Ion Movement Underlies Rectification in an Inward-Rectifier K+ Channel.
M. Spassova and Z. Lu (1998)
J. Gen. Physiol. 112, 211-221
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A Mutation in S6 of Shaker Potassium Channels Decreases the K+ Affinity of an Ion Binding Site Revealing Ion-Ion Interactions in the Pore.
E. M. Ogielska and R. W. Aldrich (1998)
J. Gen. Physiol. 112, 243-257
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Macroscopic Na+ Currents in the "Nonconducting" Shaker Potassium Channel Mutant W434F.
J. G. Starkus, L. Kuschel, M. D. Rayner, and S. H. Heinemann (1998)
J. Gen. Physiol. 112, 85-93
   Abstract »    Full Text »    PDF »
Pore mutations alter closing and opening kinetics in Shaker K+ channels.
A Molina, P Ortega-Saenz, and J Lopez-Barneo (1998)
J. Physiol. 509, 327-337
   Abstract »    Full Text »    PDF »
Distinct domains of the voltage-gated K+ channel Kvbeta 1.3 beta -subunit affect voltage-dependent gating.
V. N. Uebele, S. K. England, D. J. Gallagher, D. J. Snyders, P. B. Bennett, and M. M. Tamkun (1998)
Am J Physiol Cell Physiol 274, C1485-C1495
   Abstract »    Full Text »    PDF »
Inactivation of Voltage-Gated Cardiac K+ Channels.
R. L. Rasmusson, M. J. Morales, S. Wang, S. Liu, D. L. Campbell, M. V. Brahmajothi, and H. C. Strauss (1998)
Circ. Res. 82, 739-750
   Abstract »    Full Text »    PDF »
Time-irreversible Subconductance Gating Associated with Ba2+ Block of Large Conductance Ca2+-activated K+ Channels.
R. A. Bello and K. L. Magleby (1998)
J. Gen. Physiol. 111, 343-362
   Abstract »    Full Text »    PDF »
The Interaction of Na+ and K+ in Voltage-gated Potassium Channels: Evidence for Cation Binding Sites of Different Affinity.
L. Kiss, D. Immke, J. LoTurco, and S. J. Korn (1998)
J. Gen. Physiol. 111, 195-206
   Abstract »    Full Text »    PDF »
Killing K Channels with TEA+.
K. Khodakhah, A. Melishchuk, and C. M. Armstrong (1997)
PNAS 94, 13335-13338
   Abstract »    Full Text »    PDF »
Allosteric Effects of Permeating Cations on Gating Currents during K+ Channel Deactivation.
F. S.P. Chen, D. Steele, and D. Fedida (1997)
J. Gen. Physiol. 110, 87-100
   Abstract »    Full Text »    PDF »
Single Channel Seeks Permeant Ion for Brief but Intimate Relationship.
G. Yellen (1997)
J. Gen. Physiol. 110, 83-85
   Full Text »    PDF »
Effect of Alkali Metal Cations on Slow Inactivation of Cardiac Na+ Channels.
C. Townsend and R. Horn (1997)
J. Gen. Physiol. 110, 23-33
   Abstract »    Full Text »    PDF »
.
X. Zhang, J. W. Anderson, and D. Fedida (1997)
J. Pharmacol. Exp. Ther. 281, 1247-1256
   Abstract »    Full Text »
Frequency-Dependent Inactivation of Mammalian A-Type K+ Channel KV1.4 Regulated by Ca2+/Calmodulin-Dependent Protein Kinase.
J. Roeper, C. Lorra, and O. Pongs (1997)
J. Neurosci. 17, 3379-3391
   Abstract »    Full Text »    PDF »
Preferential Interaction of omega -Conotoxins with Inactivated N-type Ca2+ Channels.
J. W. Stocker, L. Nadasdi, R. W. Aldrich, and R. W. Tsien (1997)
J. Neurosci. 17, 3002-3013
   Abstract »    Full Text »    PDF »
Trapping of Organic Blockers by Closing of Voltage-dependent K+ Channels: Evidence for a Trap Door Mechanism of Activation Gating.
M. Holmgren, P. L. Smith, and G. Yellen (1997)
J. Gen. Physiol. 109, 527-535
   Abstract »    Full Text »    PDF »
Dihydropyridine Action on Voltage-dependent Potassium Channels Expressed in Xenopus Oocytes.
V. Avdonin, E. F. Shibata, and T. Hoshi (1997)
J. Gen. Physiol. 109, 169-180
   Abstract »    Full Text »    PDF »
Mechanism of Tetracaine Block of Cyclic Nucleotide-gated Channels.
A. A. Fodor, S. E. Gordon, and W. N. Zagotta (1997)
J. Gen. Physiol. 109, 3-14
   Abstract »    Full Text »    PDF »
Two functionally distinct subsites for the binding of internal blockers to the pore of voltage-activated K+ channels.
T. Baukrowitz and G. Yellen (1996)
PNAS 93, 13357-13361
   Abstract »    Full Text »    PDF »
Molecular Analysis of a Binding Site for Quinidine in a Human Cardiac Delayed Rectifier K+ Channel : Role of S6 in Antiarrhythmic Drug Binding.
S. W. Yeola, T. C. Rich, V. N. Uebele, M. M. Tamkun, and D. J. Snyders (1996)
Circ. Res. 78, 1105-1114
   Abstract »    Full Text »
Cations Affect the Rate of Gating Charge Recovery in Wild-type and W434F Shaker Channels through a Variety of Mechanisms.
Z. Varga, M. D. Rayner, and J. G. Starkus (2002)
J. Gen. Physiol. 119, 467-486
   Abstract »    Full Text »    PDF »


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