Simple shifts in the voltage dependence of sodium channel gating caused by divalent cations.

Hahin, Richard; Campbell, Donald T.

doi:10.1085/jgp.82.6.785

Cited by 79 publications

(62 citation statements)

References 23 publications

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“…This fact provides us with a tool to test the validity of the screening hypothesis. In our study we used the strontium ion (Sr 2þ ) as probe, because it seems to act exclusively via a screening mechanism; together with the magnesium ion (Mg 2þ ), it shifts the G(V) curve less than other tested metal ions, and activation time courses, deactivation time courses, gating currents, and G(V) curves are equally affected, as if these metal ions only alter the membrane voltage (11,15,21,22,(33)(34)(35)(36).…”

Section: Introductionmentioning

confidence: 99%

Extracellular Linkers Completely Transplant the Voltage Dependence from Kv1.2 Ion Channels to Kv2.1

Elinder

Madeja

Zeberg

et al. 2016

Biophysical Journal

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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 2þ ) 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 2þ (50 mM shifted G(V) by þ21.7 mV), and Kv2.1 to be the least sensitive (þ7.8 mV). Experiments on 25 chimeras, constructed from Kv1.2 and Kv2.1, showed that the large Sr 2þ -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 2þ 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.

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Section: Introductionmentioning

confidence: 99%

Extracellular Linkers Completely Transplant the Voltage Dependence from Kv1.2 Ion Channels to Kv2.1

Elinder

Madeja

Zeberg

et al. 2016

Biophysical Journal

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“…Among the ions that can play a role, one of the most effective in screening is calcium [7]. The variation of extracellular free calcium leads to a different screening effect on the outer side of the membrane and this in turn leads to a change in the voltage drop across the membrane, that voltage dependent channels sense and respond to [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Chondroitin Sulfates Act as Extracellular Gating Modifiers on Voltage-Dependent Ion Channels

Vigetti¹,

Andrini²,

Clerici³

et al. 2008

Cell Physiol Biochem

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Background/Aims. Chondroitin sulfates are glycosaminoglycans bound to core proteins of proteoglycans in the extracellular matrix and perineuronal nets surrounding many types of neurones. Chondroitin 4- and chondroitin 6- sulfate can bind calcium ions with different affinities, depending on their sulfation position. Extracellular calcium plays a key role in determining the transmembrane potential sensed by voltage-operated ion channels (VOCs) by means of the "surface screening effect" theory (Gouy-Chapman-Stern theory). We wanted to test whether chondroitin sulfates at physiological concentration can effectively modulate the gating properties of VOCs. Methods. We recorded in patch-clamp experiments the shift of h and voltage-dependent calcium currents activation curves of Xenopus laevis photoreceptors perfused with chondroitin sulfate solutions in physiological extracellular calcium concentration. Results. We found that chondroitin 4- and 6- sulfate, with different capabilities, can shift the activation curve of h and voltage-dependent calcium channels, compatibly with the surface screening effect theory. Conclusion. We conclude that chondroitin sulfates can alter VOCs gating by modulating the calcium concentration in the extracellular microenvironment. This phenomenon may explain why alterations in the chondroitin sulfation and abundance in the extracellular matrix are found along with altered neuronal function in pathological conditions.

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“…Indeed, early calculations 66 suggested that 1 mM of a divalent ion added to 100 mM electrolyte could shift membrane potential by ~26 mV due to the screening effect. With these considerations in mind, classical studies of ion channels have routinely documented voltage-dependent channel properties over a range of divalent ion concentrations [67][68][69] . It would seem important for the electrophysiological observations of today to account for such phenomena.…”

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confidence: 99%

Electrodiffusion phenomena in neuroscience: a neglected companion

2017

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The emerging technological revolution in genetically encoded molecular sensors and super-resolution imaging provides neuroscientists with a pass to the real-time nano-world. On this small scale, however, classical principles of electrophysiology do not always apply. This is in large part because the nanoscopic heterogeneities in ionic concentrations and the local electric fields associated with individual ions and their movement can no longer be ignored. Here, we review basic principles of molecular electrodiffusion in the cellular environment of organized brain tissue. We argue that accurate interpretation of physiological observations on the nanoscale requires a better understanding of the underlying electrodiffusion phenomena.

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Simple shifts in the voltage dependence of sodium channel gating caused by divalent cations.

Cited by 79 publications

References 23 publications

Extracellular Linkers Completely Transplant the Voltage Dependence from Kv1.2 Ion Channels to Kv2.1

Extracellular Linkers Completely Transplant the Voltage Dependence from Kv1.2 Ion Channels to Kv2.1

Chondroitin Sulfates Act as Extracellular Gating Modifiers on Voltage-Dependent Ion Channels

Electrodiffusion phenomena in neuroscience: a neglected companion

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