scholarly journals Discovery, Characterization, and Effects on Renal Fluid and Electrolyte Excretion of the Kir4.1 Potassium Channel Pore Blocker, VU0134992

2018 ◽  
Vol 94 (2) ◽  
pp. 926-937 ◽  
Author(s):  
Sujay V. Kharade ◽  
Haruto Kurata ◽  
Aaron M. Bender ◽  
Anna L. Blobaum ◽  
Eric E. Figueroa ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Electrolyte Excretion ◽  
Channel Pore ◽  
Pore Blocker

scholarly journals An Inactivation Stabilizer of the Na+ Channel Acts as an Opportunistic Pore Blocker Modulated by External Na+

2005 ◽  
Vol 125 (5) ◽  
pp. 465-481 ◽  
Author(s):  
Ya-Chin Yang ◽  
Chung-Chin Kuo
Keyword(s):  
Binding Site ◽  
Conformational Changes ◽  
Dissociation Constants ◽  
Channel Gating ◽  
Structural Motif ◽  
Na Channel ◽  
Channel Pore ◽  
Conduction Pathway ◽  
Gating Process ◽  
Pore Blocker

The Na+ channel is the primary target of anticonvulsants carbamazepine, phenytoin, and lamotrigine. These drugs modify Na+ channel gating as they have much higher binding affinity to the inactivated state than to the resting state of the channel. It has been proposed that these drugs bind to the Na+ channel pore with a common diphenyl structural motif. Diclofenac is a widely prescribed anti-inflammatory agent that has a similar diphenyl motif in its structure. In this study, we found that diclofenac modifies Na+ channel gating in a way similar to the foregoing anticonvulsants. The dissociation constants of diclofenac binding to the resting, activated, and inactivated Na+ channels are ∼880 μM, ∼88 μM, and ∼7 μM, respectively. The changing affinity well depicts the gradual shaping of a use-dependent receptor along the gating process. Most interestingly, diclofenac does not show the pore-blocking effect of carbamazepine on the Na+ channel when the external solution contains 150 mM Na+, but is turned into an effective Na+ channel pore blocker if the extracellular solution contains no Na+. In contrast, internal Na+ has only negligible effect on the functional consequences of diclofenac binding. Diclofenac thus acts as an “opportunistic” pore blocker modulated by external but not internal Na+, indicating that the diclofenac binding site is located at the junction of a widened part and an acutely narrowed part of the ion conduction pathway, and faces the extracellular rather than the intracellular solution. The diclofenac binding site thus is most likely located at the external pore mouth, and undergoes delicate conformational changes modulated by external Na+ along the gating process of the Na+ channel.

Probing a Potassium Channel Pore with an Engineered Protonatable Site

Biochemistry ◽  
1995 ◽  
Vol 34 (40) ◽  
pp. 13133-13138 ◽  
Author(s):  
Zhe Lu ◽  
Roderick MacKinnon
Keyword(s):  
Potassium Channel ◽  
Channel Pore

scholarly journals Interactions between amiodarone and the hERG potassium channel pore determined with mutagenesis and in silico docking

2016 ◽  
Vol 113 ◽  
pp. 24-35 ◽  
Author(s):  
Yihong Zhang ◽  
Charlotte K. Colenso ◽  
Aziza El Harchi ◽  
Hongwei Cheng ◽  
Harry J. Witchel ◽  
...  
Keyword(s):  
Potassium Channel ◽  
In Silico ◽  
Channel Pore ◽  
In Silico Docking

scholarly journals Identification of a trafficking determinant localized to the Kv1 potassium channel pore

2001 ◽  
Vol 98 (24) ◽  
pp. 14055-14059 ◽  
Author(s):  
L. N. Manganas ◽  
Q. Wang ◽  
R. H. Scannevin ◽  
D. E. Antonucci ◽  
K. J. Rhodes ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Channel Pore

scholarly journals A structural motif for the voltage-gated potassium channel pore.

1995 ◽  
Vol 92 (20) ◽  
pp. 9215-9219 ◽  
Author(s):  
G. M. Lipkind ◽  
D. A. Hanck ◽  
H. A. Fozzard
Keyword(s):  
Potassium Channel ◽  
Structural Motif ◽  
Channel Pore ◽  
Voltage Gated

scholarly journals MinK Residues Line a Potassium Channel Pore

Neuron ◽  
1996 ◽  
Vol 16 (3) ◽  
pp. 571-577 ◽  
Author(s):  
Ke-Wei Wang ◽  
Kwok-Keung Tai ◽  
Steve A.N Goldstein
Keyword(s):  
Potassium Channel ◽  
Channel Pore

scholarly journals Mechanism of Accelerated Current Decay Caused by an Episodic Ataxia Type-1-Associated Mutant in a Potassium Channel Pore

2011 ◽  
Vol 31 (48) ◽  
pp. 17449-17459 ◽  
Author(s):  
C. J. Peters ◽  
D. Werry ◽  
H. S. Gill ◽  
E. A. Accili ◽  
D. Fedida
Keyword(s):  
Potassium Channel ◽  
Episodic Ataxia ◽  
Channel Pore ◽  
Current Decay ◽  
Episodic Ataxia Type
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