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Biophys J
2016 Oct 18;1118:1679-1691. doi: 10.1016/j.bpj.2016.08.043.
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Extracellular Linkers Completely Transplant the Voltage Dependence from Kv1.2 Ion Channels to Kv2.1.
Elinder F, Madeja M, Zeberg H, Århem P.
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The transmembrane voltage needed to open different voltage-gated K (Kv) channels differs by up to 50 mV from each other. In this study we test the hypothesis that the channels' voltage dependences to a large extent are set by charged amino-acid residues of the extracellular linkers of the Kv channels, which electrostatically affect the charged amino-acid residues of the voltage sensor S4. Extracellular cations shift the conductance-versus-voltage curve, G(V), by interfering with these extracellular charges. We have explored these issues by analyzing the effects of the divalent strontium ion (Sr(2+)) on the voltage dependence of the G(V) curves of wild-type and chimeric Kv channels expressed in Xenopus oocytes, using the voltage-clamp technique. Out of seven Kv channels, Kv1.2 was found to be most sensitive to Sr(2+) (50 mM shifted G(V) by +21.7 mV), and Kv2.1 to be the least sensitive (+7.8 mV). Experiments on 25 chimeras, constructed from Kv1.2 and Kv2.1, showed that the large Sr(2+)-induced G(V) shift of Kv1.2 can be transferred to Kv2.1 by exchanging the extracellular linker between S3 and S4 (L3/4) in combination with either the extracellular linker between S5 and the pore (L5/P) or that between the pore and S6 (LP/6). The effects of the linker substitutions were nonadditive, suggesting specific structural interactions. The free energy of these interactions was ∼20 kJ/mol, suggesting involvement of hydrophobic interactions and/or hydrogen bonds. Using principles from double-layer theory we derived an approximate linear equation (relating the voltage shifts to altered ionic strength), which proved to well match experimental data, suggesting that Sr(2+) acts on these channels mainly by screening surface charges. Taken together, these results highlight the extracellular surface potential at the voltage sensor as an important determinant of the channels' voltage dependence, making the extracellular linkers essential targets for evolutionary selection.
Arhem,
Channel density regulation of firing patterns in a cortical neuron model.
2006, Pubmed
Arhem,
Channel density regulation of firing patterns in a cortical neuron model.
2006,
Pubmed Arhem,
Effects of some heavy metal ions on the ionic currents of myelinated fibres from Xenopus laevis.
1980,
Pubmed
,
Xenbase Arhem,
Effects of rubidium, caesium, strontium, barium and lanthanum on ionic currents in myelinated nerve fibres from Xenopus laevis.
1980,
Pubmed
,
Xenbase Arhem,
Ion channel density and threshold dynamics of repetitive firing in a cortical neuron model.
2007,
Pubmed Armstrong,
Calcium ion as a cofactor in Na channel gating.
1991,
Pubmed Armstrong,
Voltage-gated K channels.
2003,
Pubmed Börjesson,
An electrostatic potassium channel opener targeting the final voltage sensor transition.
2011,
Pubmed
,
Xenbase Börjesson,
Structure, function, and modification of the voltage sensor in voltage-gated ion channels.
2008,
Pubmed Brismar,
The effect of calcium on the potassium permeability in the myelinated nerve fibre of Xenopus laevis.
1972,
Pubmed
,
Xenbase Broomand,
Large-scale movement within the voltage-sensor paddle of a potassium channel-support for a helical-screw motion.
2008,
Pubmed
,
Xenbase Broomand,
Electrostatic domino effect in the Shaker K channel turret.
2007,
Pubmed
,
Xenbase Dani,
Lyotropic anions. Na channel gating and Ca electrode response.
1983,
Pubmed Dumont,
Oogenesis in Xenopus laevis (Daudin). I. Stages of oocyte development in laboratory maintained animals.
1972,
Pubmed
,
Xenbase Elinder,
Localization of the extracellular end of the voltage sensor S4 in a potassium channel.
2001,
Pubmed
,
Xenbase Elinder,
Surface Charges of K channels. Effects of strontium on five cloned channels expressed in Xenopus oocytes.
1996,
Pubmed
,
Xenbase Elinder,
Divalent cation effects on the Shaker K channel suggest a pentapeptide sequence as determinant of functional surface charge density.
1998,
Pubmed
,
Xenbase Elinder,
The functional surface charge density of a fast K channel in the myelinated axon of Xenopus laevis.
1998,
Pubmed
,
Xenbase Elinder,
S4 charges move close to residues in the pore domain during activation in a K channel.
2001,
Pubmed
,
Xenbase Elinder,
Effects of gadolinium on ion channels in the myelinated axon of Xenopus laevis: four sites of action.
1994,
Pubmed
,
Xenbase Elinder,
Metal ion effects on ion channel gating.
2003,
Pubmed Elinder,
Role of individual surface charges of voltage-gated K channels.
1999,
Pubmed Elinder,
The modulatory site for the action of gadolinium on surface charges and channel gating.
1994,
Pubmed
,
Xenbase Erisir,
Function of specific K(+) channels in sustained high-frequency firing of fast-spiking neocortical interneurons.
1999,
Pubmed FRANKENHAEUSER,
The action of calcium on the electrical properties of squid axons.
1957,
Pubmed FRANKENHAEUSER,
The effect of magnesium and calcium on the frog myelinated nerve fibre.
1958,
Pubmed Gilly,
Divalent cations and the activation kinetics of potassium channels in squid giant axons.
1982,
Pubmed Gilly,
Slowing of sodium channel opening kinetics in squid axon by extracellular zinc.
1982,
Pubmed Gouwens,
Synchronization of firing in cortical fast-spiking interneurons at gamma frequencies: a phase-resetting analysis.
2010,
Pubmed GRAHAME,
The electrical double layer and the theory of electrocapillarity.
1947,
Pubmed Hahin,
Simple shifts in the voltage dependence of sodium channel gating caused by divalent cations.
1983,
Pubmed Henrikson,
Identification of a surface charged residue in the S3-S4 linker of the pacemaker (HCN) channel that influences activation gating.
2003,
Pubmed
,
Xenbase Henrion,
Tracking a complete voltage-sensor cycle with metal-ion bridges.
2012,
Pubmed
,
Xenbase Hille,
Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH.
1975,
Pubmed Ho,
Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
1989,
Pubmed Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed Lyu,
G protein-gated inwardly rectifying potassium channel subunits 1 and 2 are down-regulated in rat dorsal root ganglion neurons and spinal cord after peripheral axotomy.
2015,
Pubmed Madeja,
A concentration-clamp system allowing two-electrode voltage-clamp investigations in oocytes of Xenopus laevis.
1991,
Pubmed
,
Xenbase Männikkö,
Voltage-sensing mechanism is conserved among ion channels gated by opposite voltages.
2002,
Pubmed
,
Xenbase Mathur,
Role of the S3-S4 linker in Shaker potassium channel activation.
1997,
Pubmed
,
Xenbase Ottosson,
Drug-induced ion channel opening tuned by the voltage sensor charge profile.
2014,
Pubmed
,
Xenbase Peitzsch,
Calculations of the electrostatic potential adjacent to model phospholipid bilayers.
1995,
Pubmed Prescott,
Nonlinear interaction between shunting and adaptation controls a switch between integration and coincidence detection in pyramidal neurons.
2006,
Pubmed Priest,
S3-S4 linker length modulates the relaxed state of a voltage-gated potassium channel.
2013,
Pubmed Schoppa,
The size of gating charge in wild-type and mutant Shaker potassium channels.
1992,
Pubmed Schwaiger,
The conserved phenylalanine in the K+ channel voltage-sensor domain creates a barrier with unidirectional effects.
2013,
Pubmed
,
Xenbase Smith,
Identification of common molecular subsequences.
1981,
Pubmed Smith-Maxwell,
Uncharged S4 residues and cooperativity in voltage-dependent potassium channel activation.
1998,
Pubmed
,
Xenbase Stühmer,
Potassium channels expressed from rat brain cDNA have delayed rectifier properties.
1988,
Pubmed
,
Xenbase Yu,
The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis.
2004,
Pubmed Zeberg,
Density of voltage-gated potassium channels is a bifurcation parameter in pyramidal neurons.
2015,
Pubmed Zeberg,
Ion channel density regulates switches between regular and fast spiking in soma but not in axons.
2010,
Pubmed
,
Xenbase
