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Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
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Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes

Published on: October 15, 2016

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Dual regulation of hEAG1 channels by phosphatidylinositol 4,5-bisphosphate

Mayra Delgado-Ramírez1, Angélica López-Izquierdo2, Aldo A Rodríguez-Menchaca1

  • 1Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP 78210, Mexico.

Biochemical and Biophysical Research Communications
|September 14, 2018
PubMed

Insights

Phosphatidylinositol 4,5-bisfofate (PIP2) shows dual effects on ether-à-go-go1 (EAG1) K+ channels. Its regulatory role depends on the initial plasma membrane levels, acting as both an activator and inhibitor.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biophysics

Background:

  • The ether-à-go-go1 (EAG1, Kv10.1) K+ channel is crucial in the central nervous system and cancer cells.
  • The role of membrane lipids, particularly phosphatidylinositol 4,5-bisfofate (PIP2), in regulating EAG1 channels is not well understood.

Purpose of the Study:

  • To investigate the regulatory effects of PIP2 on human EAG1 (hEAG1) channel activity.
  • To elucidate the dual role of PIP2 in modulating hEAG1 channel function.

Main Methods:

  • Utilized patch clamp electrophysiology to record hEAG1 currents.
  • Manipulated endogenous PIP2 levels using Danio rerio voltage-sensing phosphatase (Dr-VSP) and human muscarinic type-1 receptor (hM1R) activation.
  • Applied exogenous PIP2 to alter plasma membrane PIP2 concentrations.

Main Results:

  • Depletion of endogenous PIP2 by Dr-VSP or hM1R activation led to inhibition of hEAG1 currents.
  • Application of exogenous PIP2 also resulted in the inhibition of hEAG1 currents.
  • Demonstrated a concentration-dependent, dual effect of PIP2 on hEAG1 channel activity.

Conclusions:

  • PIP2 exhibits a dual regulatory role on hEAG1 channels, acting as either an activator or inhibitor.
  • The effect of PIP2 on hEAG1 channels is contingent upon its initial concentration on the plasma membrane.
  • Findings provide novel insights into the lipid modulation of voltage-gated potassium channels.
Keywords:
Ion channel regulationLipidsPatch clampPotassium channels

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