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Biophys J
2001 Nov 01;815:2606-13. doi: 10.1016/S0006-3495(01)75904-8.
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Distinct mechanisms of block of Kv1.5 channels by tertiary and quaternary amine clofilium compounds.
Steidl JV
,
Yool AJ
.
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The quaternary ammonium compound clofilium and its tertiary amine derivative LY97241 were used to analyze mechanisms of block in a voltage-gated potassium channel. Wild-type and mutant Kv1.5 channels expressed in Xenopus oocytes were recorded by two-electrode voltage clamp. Open-channel block to 20% of the control current amplitude was induced reversibly by 50 microM clofilium or 200 microM LY97241, and was seen as an acceleration of the macroscopic current decay. Although blockers remained present after application, channels recovered from block during each interpulse interval. The optimum voltage for recovery (-45 mV at pH 7.3) at the threshold for channel activation indicated that clofilium block and recovery occurred principally through the open channel state. In contrast, LY97241 appeared to exit from the closed state and the open state. In an acid-tolerant Kv1.5 mutant channel (H452Q), external pH was used to titrate LY97241. At low pH, which protonates the LY97241 amine group, recovery from block at hyperpolarized potentials was impaired in a manner similar to that seen with clofilium. Recovery from clofilium block was reduced at negative potentials independent of pH, an effect attributed to trapping of the permanently charged compound within the closed channels.
Arena,
Block of heart potassium channels by clofilium and its tertiary analogs: relationship between drug structure and type of channel blocked.
1988, Pubmed
Arena,
Block of heart potassium channels by clofilium and its tertiary analogs: relationship between drug structure and type of channel blocked.
1988,
Pubmed
Armstrong,
Inactivation of the potassium conductance and related phenomena caused by quaternary ammonium ion injection in squid axons.
1969,
Pubmed
Armstrong,
Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons.
1971,
Pubmed
Castle,
Selective inhibition of potassium currents in rat ventricle by clofilium and its tertiary homolog.
1991,
Pubmed
Choi,
The internal quaternary ammonium receptor site of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
Demo,
The inactivation gate of the Shaker K+ channel behaves like an open-channel blocker.
1991,
Pubmed
Hille,
Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction.
1977,
Pubmed
Holmgren,
Trapping of organic blockers by closing of voltage-dependent K+ channels: evidence for a trap door mechanism of activation gating.
1997,
Pubmed
Malayev,
Mechanism of clofilium block of the human Kv1.5 delayed rectifier potassium channel.
1995,
Pubmed
,
Xenbase
Miller,
Coupling of voltage-dependent gating and Ba++ block in the high-conductance, Ca++-activated K+ channel.
1987,
Pubmed
Mitcheson,
Trapping of a methanesulfonanilide by closure of the HERG potassium channel activation gate.
2000,
Pubmed
,
Xenbase
Ragsdale,
Molecular determinants of state-dependent block of Na+ channels by local anesthetics.
1994,
Pubmed
,
Xenbase
Steidl,
Differential sensitivity of voltage-gated potassium channels Kv1.5 and Kv1.2 to acidic pH and molecular identification of pH sensor.
1999,
Pubmed
,
Xenbase
Suessbrich,
Specific block of cloned Herg channels by clofilium and its tertiary analog LY97241.
1997,
Pubmed
,
Xenbase
Swanson,
Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain.
1990,
Pubmed
,
Xenbase
Woodhull,
Ionic blockage of sodium channels in nerve.
1973,
Pubmed
Yool,
Block of the inactivating potassium channel by clofilium and hydroxylamine depends on the sequence of the pore region.
1994,
Pubmed
,
Xenbase
Zhang,
LY 97241 accelerates the apparent rate of inactivation of transient outward K+ current: characterization of open channel block.
1995,
Pubmed
