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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
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Modulating Hyperpolarization-Activated Cation Currents through Small Molecule Perturbations: Magnitude and Gating

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The hyperpolarization-activated cation current (Ih) regulates electrical activity. Many compounds and herbal drugs modulate Ih magnitude and kinetics, with some suppressing and others enhancing its amplitude.

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Area of Science:

  • Electrophysiology
  • Pharmacology
  • Molecular Biology

Background:

  • The hyperpolarization-activated cation current (Ih) is crucial for electrical activity in excitable cells.
  • Numerous compounds and herbal drugs can influence Ih magnitude and gating kinetics.

Purpose of the Study:

  • To investigate the effects of various chemical compounds and herbal drugs on the hyperpolarization-activated cation current (Ih).
  • To characterize how these agents modulate Ih amplitude and voltage-dependent hysteresis.

Main Methods:

  • Electrophysiological recordings to measure Ih current.
  • Application of diverse compounds including brivaracetam, carisbamate, cilobradine, dexmedetomidine, GAL-021, lutein, pirfenidone, tramadol, oxaliplatin, and various herbal extracts.
  • Analysis of concentration- and voltage-dependent effects on Ih amplitude and hysteresis.

Main Results:

  • Brivaracetam, carisbamate, cilobradine, dexmedetomidine, GAL-021, lutein, pirfenidone, tramadol, and several herbal drugs suppressed Ih amplitude.
  • Carisbamate and lutein also reduced voltage-dependent hysteresis.
  • Oxaliplatin increased Ih amplitude.
  • Cilobradine affected delayed-rectifier K+ currents.

Conclusions:

  • Compounds and herbal drugs exhibit diverse regulatory effects on Ih.
  • Modulation of Ih by these agents contributes to their impact on cellular function.
  • Ih serves as a potential target for therapeutic interventions.