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Pioglitazone, a PPAR-γ Activator, Stimulates BK

Tsang-Shan Chen1, Ming-Chi Lai2, Te-Yu Hung2

  • 1Department of Neurology, Tainan Sin-Lau Hospital, Tainan, Taiwan.

Frontiers in Pharmacology
|September 14, 2018
PubMed
Summary

Pioglitazone stimulates Ca2+-activated K+ currents and inhibits M-type K+ currents in hippocampal neurons. These effects on potassium channels may explain its broad pharmacological actions.

Keywords:
Ca2+-activated K+ currentM-type K+ currenthippocampal neuronlarge-conductance Ca2+-activated K+ channelpioglitazone

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Pioglitazone (PIO) is a thiazolidinedione known to activate peroxisome proliferator-activated receptor-γ (PPAR-γ).
  • PIO exhibits anti-inflammatory, anti-proliferative, anti-diabetic, and antidepressive properties.
  • Its effects on specific potassium currents in central neurons are not well understood.

Purpose of the Study:

  • To investigate the impact of Pioglitazone on Ca2+-activated K+ currents (IK(Ca)) and M-type K+ currents in hippocampal neurons.
  • To elucidate the specific potassium channels affected by PIO.

Main Methods:

  • Whole-cell and inside-out patch-clamp recordings were used to measure potassium currents in mHippoE-14 cells.
  • The effects of PIO (10 μM) on IK(Ca) and M-type K+ currents were analyzed.
  • Specific channel blockers (paxilline, TRAM-39, apamin) were used to identify the type of K+ channels involved.

Main Results:

  • Pioglitazone (10 μM) significantly increased the amplitude of Ca2+-activated K+ current (IK(Ca)) in hippocampal neurons.
  • PIO's stimulation of IK(Ca) was reversed by paxilline, indicating involvement of large-conductance Ca2+-activated K+ (BKCa) channels.
  • PIO concentration-dependently activated BKCa channels (EC50 = 7.6 μM), altering their open and closed times and shifting their activation curve.
  • Pioglitazone also suppressed the amplitude of M-type K+ currents in these neurons.

Conclusions:

  • Pioglitazone modulates both Ca2+-activated K+ (specifically BKCa channels) and M-type K+ currents in hippocampal neurons.
  • These perturbations of potassium channel activity may contribute to the diverse pharmacological effects of Pioglitazone.
  • Further research into these channel interactions could reveal new therapeutic strategies.