Abstract
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 10 5 ions per second. This slow rate probably reflected the departure of the last ion from the multi-ion pore: Permeation of ions (at 10 7 per second) occurs rapidly because of ion-ion repulsion, but the last ion to leave would experience no such repulsion.
References
28
Referenced
194
-
ALMERS W, NON-SELECTIVE CONDUCTANCE IN CALCIUM CHANNELS OF FROG-MUSCLE - CALCIUM SELECTIVITY IN A SINGLE-FILE PORE, JOURNAL OF PHYSIOLOGY-LONDON 353, 585 (1984).
(
10.1113/jphysiol.1984.sp015352
) / JOURNAL OF PHYSIOLOGY-LONDON / NON-SELECTIVE CONDUCTANCE IN CALCIUM CHANNELS OF FROG-MUSCLE - CALCIUM SELECTIVITY IN A SINGLE-FILE PORE by ALMERS W (1984) -
ARMSTRONG M. C., INACTIVATION OF POTASSIUM CONDUCTANCE AND RELATED PHENOMENA CAUSED BY QUATERNARY AMMONIUM ION INJECTION IN SQUID AXONS, JOURNAL OF GENERAL PHYSIOLOGY 54, 553 (1969).
(
10.1085/jgp.54.5.553
) / JOURNAL OF GENERAL PHYSIOLOGY / INACTIVATION OF POTASSIUM CONDUCTANCE AND RELATED PHENOMENA CAUSED BY QUATERNARY AMMONIUM ION INJECTION IN SQUID AXONS by ARMSTRONG M. C. (1969) -
ARMSTRONG M. C., INTERACTION OF TETRAETHYLAMMONIUM ION DERIVATIVES WITH POTASSIUM CHANNELS OF GIANT AXONS, JOURNAL OF GENERAL PHYSIOLOGY 58, 413 (1971).
(
10.1085/jgp.58.4.413
) / JOURNAL OF GENERAL PHYSIOLOGY / INTERACTION OF TETRAETHYLAMMONIUM ION DERIVATIVES WITH POTASSIUM CHANNELS OF GIANT AXONS by ARMSTRONG M. C. (1971) -
BAUKROWITZ T, MODULATION OF K+ CURRENT BY FREQUENCY AND EXTERNAL [K+] - A TALE OF 2 INACTIVATION MECHANISMS, NEURON 15, 951 (1995).
(
10.1016/0896-6273(95)90185-X
) / NEURON / MODULATION OF K+ CURRENT BY FREQUENCY AND EXTERNAL [K+] - A TALE OF 2 INACTIVATION MECHANISMS by BAUKROWITZ T (1995) - BAUKROWITZ T unpublished data.
- BIGGER T. J., PHARM BASIS THERAPEU: CH31 (1985). / PHARM BASIS THERAPEU by BIGGER T. J. (1985)
-
BUTTERWORTH F. J., MOLECULAR MECHANISMS OF LOCAL-ANESTHESIA - A REVIEW, ANESTHESIOLOGY 72, 711 (1990).
(
10.1097/00000542-199004000-00022
) / ANESTHESIOLOGY / MOLECULAR MECHANISMS OF LOCAL-ANESTHESIA - A REVIEW by BUTTERWORTH F. J. (1990) -
CHOI L. K., THE INTERNAL QUATERNARY AMMONIUM RECEPTOR-SITE OF SHAKER POTASSIUM CHANNELS, NEURON 10, 533 (1993).
(
10.1016/0896-6273(93)90340-W
) / NEURON / THE INTERNAL QUATERNARY AMMONIUM RECEPTOR-SITE OF SHAKER POTASSIUM CHANNELS by CHOI L. K. (1993) -
CHOI L. K., TETRAETHYLAMMONIUM BLOCKADE DISTINGUISHES 2 INACTIVATION MECHANISMS IN VOLTAGE-ACTIVATED K+ CHANNELS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 88, 5092 (1991).
(
10.1073/pnas.88.12.5092
) / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA / TETRAETHYLAMMONIUM BLOCKADE DISTINGUISHES 2 INACTIVATION MECHANISMS IN VOLTAGE-ACTIVATED K+ CHANNELS by CHOI L. K. (1991) -
COLATSKY J. T., CHANNEL SPECIFICITY IN ANTIARRHYTHMIC DRUG-ACTION - MECHANISM OF POTASSIUM CHANNEL BLOCK AND ITS ROLE IN SUPPRESSING AND AGGRAVATING CARDIAC-ARRHYTHMIAS, CIRCULATION 82, 2235 (1990).
(
10.1161/01.CIR.82.6.2235
) / CIRCULATION / CHANNEL SPECIFICITY IN ANTIARRHYTHMIC DRUG-ACTION - MECHANISM OF POTASSIUM CHANNEL BLOCK AND ITS ROLE IN SUPPRESSING AND AGGRAVATING CARDIAC-ARRHYTHMIAS by COLATSKY J. T. (1990) - CRANK J, MATH DIFFUSION (1975). / MATH DIFFUSION by CRANK J (1975)
10.1016/0896-6273(91)90277-7
10.1038/309453a0
- HILLE B, IONIC CHANNELS EXCIT: CH11 (1992). / IONIC CHANNELS EXCIT by HILLE B (1992)
-
HILLE B, LOCAL-ANESTHETICS - HYDROPHILIC AND HYDROPHOBIC PATHWAYS FOR DRUG-RECEPTOR REACTION, JOURNAL OF GENERAL PHYSIOLOGY 69, 497 (1977).
(
10.1085/jgp.69.4.497
) / JOURNAL OF GENERAL PHYSIOLOGY / LOCAL-ANESTHETICS - HYDROPHILIC AND HYDROPHOBIC PATHWAYS FOR DRUG-RECEPTOR REACTION by HILLE B (1977) -
HILLE B, POTASSIUM CHANNELS AS MULTI-ION SINGLE-FILE PORES, JOURNAL OF GENERAL PHYSIOLOGY 72, 409 (1978).
(
10.1085/jgp.72.4.409
) / JOURNAL OF GENERAL PHYSIOLOGY / POTASSIUM CHANNELS AS MULTI-ION SINGLE-FILE PORES by HILLE B (1978) -
HODGKIN L. A., THE POTASSIUM PERMEABILITY OF A GIANT NERVE FIBRE, JOURNAL OF PHYSIOLOGY-LONDON 128, 61 (1955).
(
10.1113/jphysiol.1955.sp005291
) / JOURNAL OF PHYSIOLOGY-LONDON / THE POTASSIUM PERMEABILITY OF A GIANT NERVE FIBRE by HODGKIN L. A. (1955) -
HONDEGHEM M. L., CLASS-III ANTIARRHYTHMIC AGENTS HAVE A LOT OF POTENTIAL BUT A LONG WAY TO GO - REDUCED EFFECTIVENESS AND DANGERS OF REVERSE USE DEPENDENCE, CIRCULATION 81, 686 (1990).
(
10.1161/01.CIR.81.2.686
) / CIRCULATION / CLASS-III ANTIARRHYTHMIC AGENTS HAVE A LOT OF POTENTIAL BUT A LONG WAY TO GO - REDUCED EFFECTIVENESS AND DANGERS OF REVERSE USE DEPENDENCE by HONDEGHEM M. L. (1990) -
HOSHI T, 2 TYPES OF INACTIVATION IN SHAKER K+ CHANNELS - EFFECTS OF ALTERATIONS IN THE CARBOXY-TERMINAL REGION, NEURON 7, 547 (1991).
(
10.1016/0896-6273(91)90367-9
) / NEURON / 2 TYPES OF INACTIVATION IN SHAKER K+ CHANNELS - EFFECTS OF ALTERATIONS IN THE CARBOXY-TERMINAL REGION by HOSHI T (1991) 10.1126/science.2122519
- LABARCA P, BIOPHYS J 61, A378 (1992). / BIOPHYS J by LABARCA P (1992)
- LOPEZBARNEO J, EFFECTS OF EXTERNAL CATIONS AND MUTATIONS IN THE PORE REGION ON C-TYPE INACTIVATION OF SHAKER POTASSIUM CHANNELS, RECEPTORS & CHANNELS 1, 61 (1993). / RECEPTORS & CHANNELS / EFFECTS OF EXTERNAL CATIONS AND MUTATIONS IN THE PORE REGION ON C-TYPE INACTIVATION OF SHAKER POTASSIUM CHANNELS by LOPEZBARNEO J (1993)
-
MACDONALD L. R., ANTIEPILEPTIC DRUG ACTIONS, EPILEPSIA 30, S19 (1989).
(
10.1111/j.1528-1157.1989.tb05810.x
) / EPILEPSIA / ANTIEPILEPTIC DRUG ACTIONS by MACDONALD L. R. (1989) -
PARDO A. L., EXTRACELLULAR K+ SPECIFICALLY MODULATES A RAT-BRAIN K+ CHANNEL, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89, 2466 (1992).
(
10.1073/pnas.89.6.2466
) / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA / EXTRACELLULAR K+ SPECIFICALLY MODULATES A RAT-BRAIN K+ CHANNEL by PARDO A. L. (1992) -
RUPPERSBERG P. J., REGULATION OF FAST INACTIVATION OF CLONED MAMMALIAN IK(A) CHANNELS BY CYSTEINE OXIDATION, NATURE 352, 711 (1991).
(
10.1038/352711a0
) / NATURE / REGULATION OF FAST INACTIVATION OF CLONED MAMMALIAN IK(A) CHANNELS BY CYSTEINE OXIDATION by RUPPERSBERG P. J. (1991) -
STARMER F. C., MECHANISMS OF USE-DEPENDENT BLOCK OF SODIUM-CHANNELS IN EXCITABLE-MEMBRANES BY LOCAL-ANESTHETICS, BIOPHYSICAL JOURNAL 46, 15 (1984).
(
10.1016/S0006-3495(84)83994-6
) / BIOPHYSICAL JOURNAL / MECHANISMS OF USE-DEPENDENT BLOCK OF SODIUM-CHANNELS IN EXCITABLE-MEMBRANES BY LOCAL-ANESTHETICS by STARMER F. C. (1984) -
YELLEN G, AN ENGINEERED CYSTEINE IN THE EXTERNAL MOUTH OF A K+ CHANNEL ALLOWS INACTIVATION TO BE MODULATED BY METAL-BINDING, BIOPHYSICAL JOURNAL 66, 1068 (1994).
(
10.1016/S0006-3495(94)80888-4
) / BIOPHYSICAL JOURNAL / AN ENGINEERED CYSTEINE IN THE EXTERNAL MOUTH OF A K+ CHANNEL ALLOWS INACTIVATION TO BE MODULATED BY METAL-BINDING by YELLEN G (1994) -
YELLEN G, RELIEF OF NA+ BLOCK OF CA-2+-ACTIVATED K+ CHANNELS BY EXTERNAL CATIONS, JOURNAL OF GENERAL PHYSIOLOGY 84, 187 (1984).
(
10.1085/jgp.84.2.187
) / JOURNAL OF GENERAL PHYSIOLOGY / RELIEF OF NA+ BLOCK OF CA-2+-ACTIVATED K+ CHANNELS BY EXTERNAL CATIONS by YELLEN G (1984)
Dates
Type | When |
---|---|
Created | 18 years, 10 months ago (Oct. 27, 2006, 2:30 p.m.) |
Deposited | 1 year, 7 months ago (Jan. 12, 2024, 6:15 p.m.) |
Indexed | 3 weeks, 6 days ago (Aug. 2, 2025, 12:18 a.m.) |
Issued | 29 years, 6 months ago (Feb. 2, 1996) |
Published | 29 years, 6 months ago (Feb. 2, 1996) |
Published Print | 29 years, 6 months ago (Feb. 2, 1996) |
@article{Baukrowitz_1996, title={Use-Dependent Blockers and Exit Rate of the Last Ion from the Multi-Ion Pore of a K + Channel}, volume={271}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.271.5249.653}, DOI={10.1126/science.271.5249.653}, number={5249}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Baukrowitz, Thomas and Yellen, Gary}, year={1996}, month=feb, pages={653–656} }