Multiple gating modes and the effect of modulating factors on the μI sodium channel

Zhou, Jianxiong; Potts, Jerald F.; Trimmer, James S.; Agnew, William S.; Sigworth, Fred J.

doi:10.1016/0896-6273(91)90280-d

Cited by 156 publications

(152 citation statements)

References 27 publications

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“…1A). Our data show that co-expression of the /I1 and the a subunit produce the same effects as the unknown factor in the low molecular weight mRNA [2]. When the p, subunit is co-expressed with the a subunit, the equilibrium between gating modes appears shifted such that the faster gating mode dominates.…”

Section: Febs Letters July 1993mentioning

confidence: 58%

“…These channels exhibited fast gating behavior and the single channel conductance was 21 pS (Fig. 2B) which is identical to the single-channel conductance of the a subunit alone [2,8].…”

Section: Febs Letters July 1993mentioning

confidence: 78%

“…When the p, subunit is co-expressed with the a subunit, the equilibrium between gating modes appears shifted such that the faster gating mode dominates. These two types of macroscopic inactivation arise from gating mode shifts and not from multiple populations of ion channels being expressed since they are seen in patches with a single channel [2].…”

Section: Febs Letters July 1993mentioning

confidence: 99%

“…Co-expression of brain or muscle recombinant Na+ channel a subunit with low molecular weight mRNA in Xenopus oocytes induces a fast (normal) gating mode and increases the macroscopic Na' current without changing the single channel conductance [1,2]. It has been speculated that a modulatory factor encoded in the low molecular weight mRNA may be an enzyme or an accessory peptide such as a p subunit [3].…”

Section: Introductionmentioning

confidence: 99%

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A molecular basis for gating mode transitions in human skeletal muscle Na⁺ channels

1993

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Recombinant sodium channel α subunits expressed in Xenopus oocytes display an anomalously slow rate of inactivation that arises from channels that predominantly exist in a slow gating mode [1,2]. Co‐expression of Na− channel β1 subunit with the human skeletal muscle Na+ channel α subunit increases the Na+ current and induces normal gating behavior in Xenopus laevis oocytes. The effects of the β1 subunit can be explained by an allosterically induced conformational switch of the α subunit protein that occurs upon binding the β1 subunit. This binding alters the free energy barriers separating distinct conformational states of the channel. The results illustrate a fundamental modulation of ion channel gating at the molecular level, and specifically demonstrate the importance of the β1 subunit for gating mode changes of Na+ channels.

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Section: Febs Letters July 1993mentioning

confidence: 58%

“…These channels exhibited fast gating behavior and the single channel conductance was 21 pS (Fig. 2B) which is identical to the single-channel conductance of the a subunit alone [2,8].…”

Section: Febs Letters July 1993mentioning

confidence: 78%

Section: Febs Letters July 1993mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A molecular basis for gating mode transitions in human skeletal muscle Na⁺ channels

1993

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“…The opening of sodium channels is preceded by multiple voltage-dependent transitions between closed states and closed-inactivated states that may occur in parallel pathways during the activation process (Armstrong and Bezanilla, 1977;Vandenberg and Bezanilla, 1991;Correa et al, 1992;Sigworth, 1994). In addition, unmodified sodium channels have been shown to be able to switch among multiple gating modes, which differ in both activation and inactivation kinetics (Armstrong and Bezanilla, 1977;Zhou et al, 1991;Hebert et al, 1994). These different kinetic possibilities may give rise to different conformational states that may bind preferentially different toxins.…”

mentioning

confidence: 99%

Depolarization Differentially Affects Allosteric Modulation by Neurotoxins of Scorpion α‐Toxin Binding on Voltage‐Gated Sodium Channels

Cestèle¹,

Gordon²

1998

Journal of Neurochemistry

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Abstract:Voltage-gated sodium channels serve as a target for many neurotoxins that bind to several distinct, allosterically interacting receptor sites. We examined the effect of membrane potentials (incited by increasing external K~concentrations) on the binding modulation by veratridine, brevetoxin, and tetrodotoxin of the scorpion a-toxin AaH II to receptor site 3 on sodium channels of rat brain synaptosomes. Depolarization is shown to differentially modulate neurotoxin effects on AaH II binding: Veratridine increase is potentiated, brevetoxin's inhibitory effect is reduced, and tetrodotoxin enhancement is evident mainly at resting membrane potential (5 mM K~). Both tetrodotoxin and veratridine apparently reverse the inhibition of AaH II binding by brevetoxin at resting membrane potential, but only veratridine is able to partially restore AaH II binding at 0 mV (135 mM K~). Thus, the allosteric interactions are grouped into two categories, depending on the membrane potential. Under depolarized conditions, the cooperative effects among veratridine and brevetoxin on AaH II binding fit the previously described two-state conformational model. At resting membrane potential, additional interactions are revealed, which may be explained by assuming that toxin binding induces conformational changes on the channel structure, in addition to being state-dependent. Our results provide a new insight into neurotoxin action and the complex dynamic changes underlying allosteric coupling of neurotoxin receptor sites, which may be related to channel gating. Key Words: Allosteric interactionsNeurotoxins-Sodium channels-Scorpion a-toxinBrevetoxin.

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Electrophysiological characterization of voltage-gated Na+ current expressed in the highly metastatic Mat-LyLu cell line of rat prostate cancer

Grimes

Djamgoz

1998

J. Cell. Physiol.

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Voltage-gated Na+ channels, classically associated with impulse conduction in excitable tissues, are also found in a variety of epithelial cell types where their possible functions are not known so well. We have previously reported expression of a voltage-gated Na+ channel specifically in the highly metastatic Mat-LyLu rat prostate cancer cell line; blockage of the current with tetrodotoxin (TTX) significantly reduced the invasiveness of the cells in vitro, suggesting that the channel may have a functional role in metastasis. The aim of the present study was to characterize this current using the whole-cell patch clamp recording technique, and compare it to Na+ currents found in various other tissues. The inward current of the Mat-LyLu cells was abolished completely, but reversibly, in Na+-free solution, confirming that Na+ was indeed the permeant ion. Activation occurred at -40 mV and currents reached a maximal amplitude at around 6 mV. Boltzmann fits to current activation and steady-state inactivation revealed that the currents were half activated at about -15 mV and half inactivated at -80 mV. Both current inactivation and recovery from inactivation followed a double-exponential time course with fast and slow components. The Na+ currents were highly sensitive to block by TTX (IC50 approximately 18 nM), whilst 1 microM mu-conotoxin GIIIA mostly had no effect. 100 microM Cd2+ also had no effect on the current, whilst 2.5 mM Cd2+, Mn2+, and Co2+ each caused a depolarizing shift in activation and a reduction in peak conductance of around 20%. In conclusion, the Na+ channel expressed in the highly metastatic Mat-LyLu cell line appeared to have electrophysiological and pharmacological properties of TTX-sensitive channels. Further work is needed, however, to elucidate the exact nature of the channel protein and the mechanism(s) of its involvement in cellular invasiveness.

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Multiple gating modes and the effect of modulating factors on the μI sodium channel

Cited by 156 publications

References 27 publications

A molecular basis for gating mode transitions in human skeletal muscle Na⁺ channels

A molecular basis for gating mode transitions in human skeletal muscle Na⁺ channels

Depolarization Differentially Affects Allosteric Modulation by Neurotoxins of Scorpion α‐Toxin Binding on Voltage‐Gated Sodium Channels

Electrophysiological characterization of voltage-gated Na+ current expressed in the highly metastatic Mat-LyLu cell line of rat prostate cancer

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Multiple gating modes and the effect of modulating factors on the μI sodium channel

Cited by 156 publications

References 27 publications

A molecular basis for gating mode transitions in human skeletal muscle Na+ channels

A molecular basis for gating mode transitions in human skeletal muscle Na+ channels

Depolarization Differentially Affects Allosteric Modulation by Neurotoxins of Scorpion α‐Toxin Binding on Voltage‐Gated Sodium Channels

Electrophysiological characterization of voltage-gated Na+ current expressed in the highly metastatic Mat-LyLu cell line of rat prostate cancer

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A molecular basis for gating mode transitions in human skeletal muscle Na⁺ channels

A molecular basis for gating mode transitions in human skeletal muscle Na⁺ channels