scholarly journals The conserved potassium channel filter can have distinct ion binding profiles: Structural analysis of rubidium, cesium, and barium binding in NaK2K

2014 ◽  
Vol 144 (2) ◽  
pp. 181-192 ◽  
Author(s):  
Yee Ling Lam ◽  
Weizhong Zeng ◽  
David Bryant Sauer ◽  
Youxing Jiang
Keyword(s):  
Structural Analysis ◽  
Single Channel ◽  
Ion Binding ◽  
Monovalent Cations ◽  
Binding Properties ◽  
Structural Explanation ◽  
The Difference ◽  
Extracellular Side ◽  
Lock In ◽  
External K

Potassium channels are highly selective for K+ over the smaller Na+. Intriguingly, they are permeable to larger monovalent cations such as Rb+ and Cs+ but are specifically blocked by the similarly sized Ba2+. In this study, we used structural analysis to determine the binding profiles for these permeant and blocking ions in the selectivity filter of the potassium-selective NaK channel mutant NaK2K and also performed permeation experiments using single-channel recordings. Our data revealed that some ion binding properties of NaK2K are distinct from those of the canonical K+ channels KcsA and MthK. Rb+ bound at sites 1, 3, and 4 in NaK2K, as it does in KcsA. Cs+, however, bound predominantly at sites 1 and 3 in NaK2K, whereas it binds at sites 1, 3, and 4 in KcsA. Moreover, Ba2+ binding in NaK2K was distinct from that which has been observed in KcsA and MthK, even though all of these channels show similar Ba2+ block. In the presence of K+, Ba2+ bound to the NaK2K channel at site 3 in conjunction with a K+ at site 1; this led to a prolonged block of the channel (the external K+-dependent Ba2+ lock-in state). In the absence of K+, however, Ba2+ acts as a permeating blocker. We found that, under these conditions, Ba2+ bound at sites 1 or 0 as well as site 3, allowing it to enter the filter from the intracellular side and exit from the extracellular side. The difference in the Ba2+ binding profile in the presence and absence of K+ thus provides a structural explanation for the short and prolonged Ba2+ block observed in NaK2K.

scholarly journals Temperature dependence of ion permeation at the endplate channel.

1983 ◽  
Vol 81 (5) ◽  
pp. 687-703 ◽  
Author(s):  
H M Hoffmann ◽  
V E Dionne
Keyword(s):  
Free Energy ◽  
Single Channel ◽  
Ion Selectivity ◽  
Boltzmann Distribution ◽  
Type Model ◽  
Fluctuation Analysis ◽  
Ion Binding ◽  
Ion Permeation ◽  
Channel Conductance ◽  
Extracellular Side

The dependence of acetylcholine receptor mean single-channel conductance on temperature was studied at garter snake twitch-muscle endplates using fluctuation analysis. In normal saline under conditions where most of the endplate current was carried by Na+, the channel conductance increased continuously from near 0 degrees C to approximately 23 degrees C with a Q10 of 1.97 +/- 0.14 (mean +/- SD). When 50% of the bath Na+ was replaced by either Li+, Rb+, or Cs+, the Q10 did not change significantly; however, at any temperature the channel conductance was greatest in Cs-saline and decreased with the ion sequence Cs greater than Rb greater than Na greater than Li. The results were fit by an Eyring-type model consisting of one free-energy well on the extracellular side of a single energy barrier. Ion selectivity appeared to result from ion-specific differences in the well and not in the barrier of this model. With a constant barrier enthalpy for different ions, well free-energy depth was greatest for Cs+ and graded identical to the permeability sequence. The correlation between increased well depth (i.e., ion binding) and increased channel conductance can be accounted for by the Boltzmann distribution of thermal energy.

scholarly journals Permeation of internal and external monovalent cations through the catfish cone photoreceptor cGMP-gated channel.

1995 ◽  
Vol 106 (3) ◽  
pp. 485-505 ◽  
Author(s):  
L W Haynes
Keyword(s):  
Single Channel ◽  
Dissociation Constants ◽  
Reversal Potential ◽  
Theory Model ◽  
Rate Theory ◽  
Monovalent Cations ◽  
Common Reference ◽  
Gated Channel ◽  
Extracellular Side ◽  
Cytoplasmic Side

The permeation of monovalent cations through the cGMP-gated channel of catfish cone outer segments was examined by measuring permeability and conductance ratios under biionic conditions. For monovalent cations presented on the cytoplasmic side of the channel, the permeability ratios with respect to extracellular Na followed the sequence NH4 > K > Li > Rb = Na > Cs while the conductance ratios at +50 mV followed the sequence Na approximately NH4 > K > Rb > Li = Cs. These patterns are broadly similar to the amphibian rod channel. The symmetry of the channel was tested by presenting the test ion on the extracellular side and using Na as the common reference ion on the cytoplasmic side. Under these biionic conditions, the permeability ratios with respect to Na at the intracellular side followed the sequence NH4 > Li > K > Na > Rb > Cs while the conductance ratios at +50 mV followed the sequence NH4 > K approximately Na > Rb > Li > Cs. Thus, the channel is asymmetric with respect to external and internal cations. Under symmetrical 120 mM ionic conditions, the single-channel conductance at +50 mV ranged from 58 pS in NH4 to 15 pS for Cs and was in the order NH4 > Na > K > Rb > Cs. Unexpectedly, the single-channel current-voltage relation showed sufficient outward rectification to account for the rectification observed in multichannel patches without invoking voltage dependence in gating. The concentration dependence of the reversal potential for K showed that chloride was impermeant. Anomalous mole fraction behavior was not observed, nor, over a limited concentration range, were multiple dissociation constants. An Eyring rate theory model with a single binding site was sufficient to explain these observations.

scholarly journals Structure, function, and ion-binding properties of a K+ channel stabilized in the 2,4-ion–bound configuration

2019 ◽  
Vol 116 (34) ◽  
pp. 16829-16834 ◽  
Author(s):  
Cholpon Tilegenova ◽  
D. Marien Cortes ◽  
Nermina Jahovic ◽  
Emily Hardy ◽  
Parameswaran Hariharan ◽  
...  
Keyword(s):  
Single Channel ◽  
Ion Selectivity ◽  
Streaming Potential ◽  
Point Of View ◽  
Selectivity Filter ◽  
K Channel ◽  
Crystallographic Structure ◽  
Ion Binding ◽  
Coupled Transport ◽  
Binding Properties

Here, we present the atomic resolution crystallographic structure, the function, and the ion-binding properties of the KcsA mutants, G77A and G77C, that stabilize the 2,4-ion–bound configuration (i.e., water, K+, water, K+-ion–bound configuration) of the K+ channel’s selectivity filter. A full functional and thermodynamic characterization of the G77A mutant revealed wild-type–like ion selectivity and apparent K+-binding affinity, in addition to showing a lack of C-type inactivation gating and a marked reduction in its single-channel conductance. These structures validate, from a structural point of view, the notion that 2 isoenergetic ion-bound configurations coexist within a K+ channel’s selectivity filter, which fully agrees with the water–K+-ion–coupled transport detected by streaming potential measurements.

Causation, Explanation, and the Metaphysics of Aspect

2018 ◽  
Author(s):  
Bradford Skow
Keyword(s):  
Background Condition ◽  
Structural Explanation ◽  
Levels Of Explanation ◽  
Lexical Aspect ◽  
The Third ◽  
Main Verb ◽  
The Difference ◽  
In Virtue Of

This book aims to answer the following questions: what is the difference between a cause and a background condition? What is it to manifest a disposition? Can dispositions be extrinsic? What is the most basic kind of causation? And, what might a structural explanation be? Each chapter takes up a subset of these questions; the chapters are written to be readable independently. The answers defended rely on three ideas. Two of those ideas use a distinction from the study of lexical aspect, namely the distinction between stative verbs and non-stative verbs. The first idea is that events go with non-stative verbs, in the sense that “If S, then an event occurred in virtue of the fact that S” is true when the main verb in the clause going in for “S” is non-stative. The second is that acting, doing something, goes with non-stative verbs, in the sense that “In Ving X did something” is true iff V is a non-stative verb. The third idea is about levels of explanation: “(A because B) because C” does not entail “A because C.”

scholarly journals Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps

2014 ◽  
Vol 143 (4) ◽  
pp. 449-464 ◽  
Author(s):  
Natascia Vedovato ◽  
David C. Gadsby
Keyword(s):  
Binding Site ◽  
Single Molecule ◽  
Conformational Changes ◽  
Outward Current ◽  
Side Chain ◽  
Ion Binding ◽  
Inward Current ◽  
Na Release ◽  
K Transport ◽  
External K

A single Na+/K+-ATPase pumps three Na+ outwards and two K+ inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na+ than K+ generates outward current across the cell membrane. Less well understood is the ability of Na+/K+ pumps to generate an inward current of protons. Originally noted in pumps deprived of external K+ and Na+ ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K+ and Na+ concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na+ release from phosphorylated Na+/K+ pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na+/K+ pumps that enables proton import is not required for completion of the 3 Na+/2 K+ transport cycle. However, the back-step occurs readily during Na+/K+ transport when external K+ ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na+-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na+ and K+ ions that passes through binding site II. The inferred occurrence of Na+/K+ exchange and H+ import during the same conformational cycle of a single molecule identifies the Na+/K+ pump as a hybrid transporter. Whether Na+/K+ pump–mediated proton inflow may have any physiological or pathophysiological significance remains to be clarified.

Monaural Versus Binaural Discrimination for Normal Listeners

1963 ◽  
Vol 6 (3) ◽  
pp. 263-269 ◽  
Author(s):  
Richard G. Chappell ◽  
James F. Kavanagh ◽  
Stanley Zerlin
Keyword(s):  
Single Channel ◽  
Normal Hearing ◽  
Dual Channel ◽  
Recording Session ◽  
Monosyllabic Words ◽  
Image Separation ◽  
Test Materials ◽  
The Difference

Normal hearing adults demonstrated approximately 20% better intelligibility scores for monosyllabic words presented binaurally (with a background of conversation) than to these words presented monaurally. The test materials were recorded on dual-channel tape through two head-mounted microphones. These microphones were directed toward each of three speakers who in turn produced the monosyllabic words while two simultaneous conversations were carried on by four other participants. Throughout the recording session the experimenters attempted to preserve as naturalistic a situation as possible. The 18 subjects with normal hearing listened through earphones to a single channel of this tape presented monaurally and to both channels delivered binaurally. The difference between the monaural and binaural intelligibility scores is discussed in terms of image-separation in space.

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