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Molecular Mechanisms of Voltage-Gating and Modulation in Ion Channels

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 769

Special Issue Editor


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Guest Editor
Department of Physiology, Midwestern University, Glendale, AZ 85308, USA
Interests: ion channels; cell excitability; photomodulation

Special Issue Information

Dear Colleagues,

Voltage-gated ion channels are membrane proteins whose activity directly modifies the membrane potential of cells by allowing for a selective ion flow across the cell membrane. These ion channels have their activity (open/close probability) modulated by the cell membrane’s potential. In this fashion, voltage-gated ion channels participate in a very short loop of mechanistic feedback, in that the ion current that they generate instantly changes the membrane potential, which, in turn, directly modulates the channels’ activity through their own built-in voltage sensors. Many aspects of these channels’ voltage sensitivities, coupling, and modulation are still only partially understood or are yet to be discovered. Intramolecular and intermolecular mechanisms involving these channels are yet to be unveiled and framed as drug targets for research and development, as well as for potential therapeutics. MDPI, with myself as a Guest Editor, is launching this Special Issue, titled ‘Molecular Mechanisms of Voltage-Gating and Modulation in Ion Channels’, with the intention to produce a substantially beneficial and attractive collection of papers that will begin to close mechanistic gaps in the field of voltage-gated ion channels.

This Special Issue is led by Dr. Joao Luis Carvalho de Souza as Guest Editor and assisted by Dr. Carlos Bassetto from UTSA.

Dr. Joao Luis Carvalho de Souza
Guest Editor

Manuscript Submission Information

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Keywords

  • voltage-gated ion channels
  • voltage sensing
  • voltage sensor coupling
  • new modulators
  • ion channel modulation
  • cell excitability

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Published Papers (1 paper)

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Research

20 pages, 2793 KB  
Article
Modulation of Voltage-Gated Sodium Channels from Sensory Neurons by Isoeugenol
by David Ghim, Jehan Dib, Luiz Moreira-Junior and Joao Carvalho-de-Souza
Int. J. Mol. Sci. 2025, 26(16), 7734; https://doi.org/10.3390/ijms26167734 - 10 Aug 2025
Viewed by 623
Abstract
Isoeugenol is a phenylpropanoid that is commonly found in essential oils and has been commonly used as a flavoring agent in the culinary field and an anesthetic in fish. Yet despite its similarity to well-known eugenol, there is a lack of data regarding [...] Read more.
Isoeugenol is a phenylpropanoid that is commonly found in essential oils and has been commonly used as a flavoring agent in the culinary field and an anesthetic in fish. Yet despite its similarity to well-known eugenol, there is a lack of data regarding how isoeugenol would directly modulate neuronal excitability to interfere with pain signaling. Here, we studied the effects of isoeugenol on voltage-activated Na+ currents (INa) as a means of starting to close the gap regarding the inhibitory properties of isoeugenol on neuronal excitability. We used rat dorsal root ganglia neurons under whole cell voltage clamp for the isolation of INa.. We show that isoeugenol effectively inhibits INa fully, reversibly, and in a dose-dependent manner. Our detailed analysis also indicates the direct interaction of isoeugenol with voltage-gated Na+ channels (VGSC) is likely state-dependent, as the inhibitory activity is enhanced by membrane depolarization. This effect is beneficial for pain management, as the drug would act more effectively as neuronal activity is promoted by membrane depolarization. Our data indicates a direct inhibition of VGSC by isoeugenol might constitute the main mechanism whereby this phenylpropanoid produces analgesia. This study serves as a basis for future approaches to deeply investigate the therapeutic potential of this drug or its derivatives. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Voltage-Gating and Modulation in Ion Channels)
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