scholarly journals Cross Talk between Activation and Slow Inactivation Gates of Shaker Potassium Channels

2006 ◽  
Vol 128 (5) ◽  
pp. 547-559 ◽  
Author(s):  
Gyorgy Panyi ◽  
Carol Deutsch
Keyword(s):  
Potassium Channels ◽  
Cross Talk ◽  
Cysteine Residue ◽  
Slow Inactivation ◽  
Fundamental Factor ◽  
Functional Assays ◽  
Activation Gate ◽  
The Status ◽  
Shaker Potassium Channels ◽  
Rate Of Activation

This study addresses the energetic coupling between the activation and slow inactivation gates of Shaker potassium channels. To track the status of the activation gate in inactivated channels that are nonconducting, we used two functional assays: the accessibility of a cysteine residue engineered into the protein lining the pore cavity (V474C) and the liberation by depolarization of a Cs+ ion trapped behind the closed activation gate. We determined that the rate of activation gate movement depends on the state of the inactivation gate. A closed inactivation gate favors faster opening and slower closing of the activation gate. We also show that hyperpolarization closes the activation gate long before a channel recovers from inactivation. Because activation and slow inactivation are ubiquitous gating processes in potassium channels, the cross talk between them is likely to be a fundamental factor in controlling ion flux across membranes.

scholarly journals Probing the Cavity of the Slow Inactivated Conformation of Shaker Potassium Channels

2007 ◽  
Vol 129 (5) ◽  
pp. 403-418 ◽  
Author(s):  
Gyorgy Panyi ◽  
Carol Deutsch
Keyword(s):  
Potassium Channels ◽  
Binding Site ◽  
Conformational Change ◽  
Marked Decrease ◽  
Selectivity Filter ◽  
Slow Inactivation ◽  
Voltage Gated ◽  
Activation Gate ◽  
Shaker Potassium Channels

Slow inactivation involves a local rearrangement of the outer mouth of voltage-gated potassium channels, but nothing is known regarding rearrangements in the cavity between the activation gate and the selectivity filter. We now report that the cavity undergoes a conformational change in the slow-inactivated state. This change is manifest as altered accessibility of residues facing the aqueous cavity and as a marked decrease in the affinity of tetraethylammonium for its internal binding site. These findings have implications for global alterations of the channel during slow inactivation and putative coupling between activation and slow-inactivation gates.

scholarly journals Voltage Dependence of Slow Inactivation in Shaker Potassium Channels Results from Changes in Relative K+ and Na+ Permeabilities

2000 ◽  
Vol 115 (2) ◽  
pp. 107-122 ◽  
Author(s):  
John G. Starkus ◽  
Stefan H. Heinemann ◽  
Martin D. Rayner
Keyword(s):  
Potassium Channels ◽  
Outward Current ◽  
Negative Slope ◽  
Voltage Sensitivity ◽  
Slow Inactivation ◽  
Shaker Channels ◽  
Outward Currents ◽  
Voltage Dependent ◽  
Na Ions ◽  
Shaker Potassium Channels

Time constants of slow inactivation were investigated in NH2-terminal deleted Shaker potassium channels using macro-patch recordings from Xenopus oocytes. Slow inactivation is voltage insensitive in physiological solutions or in simple experimental solutions such as K+o//K+i or Na+o//K+i. However, when [Na+]i is increased while [K+]i is reduced, voltage sensitivity appears in the slow inactivation rates at positive potentials. In such solutions, the I-V curves show a region of negative slope conductance between ∼0 and +60 mV, with strongly increased outward current at more positive voltages, yielding an N-shaped curvature. These changes in peak outward currents are associated with marked changes in the dominant slow inactivation time constant from ∼1.5 s at potentials less than approximately +60 mV to ∼30 ms at more than +150 mV. Since slow inactivation in Shaker channels is extremely sensitive to the concentrations and species of permeant ions, more rapid entry into slow inactivated state(s) might indicate decreased K+ permeation and increased Na+ permeation at positive potentials. However, the N-shaped I-V curve becomes fully developed before the onset of significant slow inactivation, indicating that this N-shaped I-V does not arise from permeability changes associated with entry into slow inactivated states. Thus, changes in the relative contributions of K+ and Na+ ions to outward currents could arise either: (a) from depletions of [K+]i sufficient to permit increased Na+ permeation, or (b) from voltage-dependent changes in K+ and Na+ permeabilities. Our results rule out the first of these mechanisms. Furthermore, effects of changing [K+]i and [K+]o on ramp I-V waveforms suggest that applied potential directly affects relative permeation by K+ and Na+ ions. Therefore, we conclude that the voltage sensitivity of slow inactivation rates arises indirectly as a result of voltage-dependent changes in the ion occupancy of these channels, and demonstrate that simple barrier models can predict such voltage-dependent changes in relative permeabilities.

Mechanisms of the inhibition of Shaker potassium channels by protons

2003 ◽  
Vol 447 (1) ◽  
pp. 44-54 ◽  
Author(s):  
John G. Starkus ◽  
Zoltan Varga ◽  
Roland Sch�nherr ◽  
Stefan H. Heinemann
Keyword(s):  
Potassium Channels ◽  
Shaker Potassium Channels

scholarly journals Plasma exosome-derived microRNAs expression profiling and bioinformatics analysis under cross-talk between increased low-density lipoprotein cholesterol level and ATP-sensitive potassium channels variant rs1799858

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Cheng Liu ◽  
Yanxian Lai ◽  
Songsong Ying ◽  
Junfang Zhan ◽  
Yan Shen
Keyword(s):  
Potassium Channels ◽  
Expression Profile ◽  
Cross Talk ◽  
Target Genes ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Abstract Background Exosome-derived microRNAs (exo-miRs) as messengers play important roles, in the cross-talk between genetic [ATP-sensitive potassium channels (KATP) genetic variant rs1799858] and environmental [elevated serum low-density lipoprotein cholesterol (LDL-C) level] factors, but the plasma exo-miRs expression profile and its role in biological processes from genotype to phenotype remain unclear. Methods A total of 14 subjects with increased LDL-C serum levels (≥ 1.8 mmol/L) were enrolled in the study. The KATP rs1799858 was genotyped by the Sequenom MassARRAY system. The plasma exo-miRs expression profile was identified by next-generation sequencing. Results 64 exo-miRs were significantly differentially expressed (DE), among which 44 exo-miRs were up-regulated and 20 exo-miRs were down-regulated in those subjects carrying T-allele (TT + CT) of rs1799858 compared to those carrying CC genotype. The top 20 up-regulated DE-exo-miRs were miR-378 family, miR-320 family, miR-208 family, miR-483-5p, miR-22-3p, miR-490-3p, miR-6515-5p, miR-31-5p, miR-210-3p, miR-17-3p, miR-6807-5p, miR-497-5p, miR-33a-5p, miR-3611 and miR-126-5p. The top 20 down-regulated DE-exo-miRs were let-7 family, miR-221/222 family, miR-619-5p, miR-6780a-5p, miR-641, miR-200a-5p, miR-581, miR-605-3p, miR-548ar-3p, miR-135a-3p, miR-451b, miR-509-3-5p, miR-4664-3p and miR-224-5p. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently implemented to identify the top 10 DE-exo-miRs related specific target genes and signaling pathways. Only 5 DE-exo-miRs were validated by qRT-PCR as follows: miR-31-5p, miR-378d, miR-619-5p, miR-320a-3p and let-7a-5p (all P < 0.05). Conclusion These results firstly indicated the plasma exo-miRs expression profile bridging the link between genotype (KATP rs1799858) and phenotype (higher LDL-C serum level), these 5 DE-exo-miRs may be potential target intermediates for molecular intervention points.

scholarly journals Desensitization of Mouse Nicotinic Acetylcholine Receptor Channels

1998 ◽  
Vol 112 (2) ◽  
pp. 181-197 ◽  
Author(s):  
Anthony Auerbach ◽  
Gustav Akk
Keyword(s):  
Acetylcholine Receptor ◽  
Rate Constant ◽  
Binding Sites ◽  
Single Channel ◽  
Ion Permeation ◽  
Activation Gate ◽  
The Status ◽  
Single Channel Currents ◽  
Cyclic Models ◽  
Channel Currents

The rate constants of acetylcholine receptor channels (AChR) desensitization and recovery were estimated from the durations and frequencies of clusters of single-channel currents. Diliganded-open AChR desensitize much faster than either unliganded- or diliganded-closed AChR, which indicates that the desensitization rate constant depends on the status of the activation gate rather than the occupancy of the transmitter binding sites. The desensitization rate constant does not change with the nature of the agonist, the membrane potential, the species of permeant cation, channel block by ACh, the subunit composition (ε or γ), or several mutations that are near the transmitter binding sites. The results are discussed in terms of cyclic models of AChR activation, desensitization, and recovery. In particular, a mechanism by which activation and desensitization are mediated by two distinct, but interrelated, gates in the ion permeation pathway is proposed.

scholarly journals External barium influences the gating charge movement of Shaker potassium channels

1997 ◽  
Vol 72 (1) ◽  
pp. 77-84 ◽  
Author(s):  
R.S. Hurst ◽  
M.J. Roux ◽  
L. Toro ◽  
E. Stefani
Keyword(s):  
Potassium Channels ◽  
Charge Movement ◽  
Gating Charge ◽  
Shaker Potassium Channels
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