Archives of Toxicology

, Volume 86, Issue 5, pp 713–723 | Cite as

The inhibition by di(2-ethylhexyl)-phthalate of erg-mediated K+ current in pituitary tumor (GH3) cells

  • Sheng-Nan Wu
  • Wei-Hsin Yang
  • Chia-Chen Yeh
  • Hsien-Ching Huang
Molecular Toxicology
First Online:
Received:
Accepted:

Abstract

DEHP (bis(2-ethylhexyl)-phthalate) known to be an endocrine-disrupting chemical is a widely used phthalate. Little information regarding the effects of phthalate esters on ion currents is available. In this study, the effects of DEHP and other phthalate esters (DBEP: di(2-butoxyethyl)-phthalate and DMGP: di(2-methylglycol)-phthalate) on ion currents were investigated in pituitary GH3 cells. Hyperpolarization-elicited K+ currents in GH3 cells bathed in high-K+, Ca2+-free solution were examined to evaluate the effects of DEHP, DBEP, and DMGP on the ether-à-go–go-related-gene (erg) K+ current (I K(erg)). Addition of DEHP to GH3 cells suppressed the amplitude of I K(erg) in a concentration-dependent manner with an IC50 value of 16.3 μM. With a two-pulse protocol, addition of DEHP shifted the activation curve of I K(erg) to a depolarized potential by approximately 10 mV with no change in the rate of I K(erg) deactivation. This compound did not have any effects on delayed rectifier K+ current in GH3 cells, while 4-aminopyridine-3-methanol (100 μM) suppressed this current significantly. DBEP (30 μM) had little or no effect on I K(erg), while DMGP (30 μM) slightly reduced it. In inside-out configuration, DEHP (30 μM) applied to the bath slightly reduced the activity of large-conductance Ca2+-activated K+ channels. DEHP (30 μM) increased the frequency of spontaneous action potentials (APs); however, this compound at the same concentration had no effect on AP firing in KCNH2 siRNA-transfected GH3 cells. The effects described herein can contribute to their actions on functional activity of endocrine or neuroendocrine cells if similar results are found in vivo.

Keywords

di(2-ethylhexyl)-phthalate GH3 cells erg current K+ current 

Abbreviations

4-AP-3-MeOH

4-aminopyridine-3-methanol

AP

Action potential

BKCa

Channel, large-conductance Ca2+-activated K+ channel

DBEP

di(2-butoxyethyl)-phthalate

DEHP

di(2-ethylhexyl)-phthalate

DMGP

di(2-methylglycol)-phthalate

erg

ether-à-go–go-related gene

IK(DR)

Delayed rectifier K+ current

IK(erg)

erg-mediated K+ current

I–V

Current-voltage

SEM

Standard error of mean

siRNA

Short-interfering RNA

TTX

Tetrodotoxin

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Notes

Acknowledgments

The project in this laboratory was supported by a grant from the National Science Council (NSC-98-2320-B-006-MY3).

Conflict of interest

The authors declare no competing interests in this work.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Sheng-Nan Wu
    • 1
    • 2
    • 3
  • Wei-Hsin Yang
    • 1
  • Chia-Chen Yeh
    • 1
  • Hsien-Ching Huang
    • 1
  1. 1.Department of PhysiologyNational Cheng Kung University Medical CollegeTainan CityTaiwan
  2. 2.Department of Anatomy and Cell BiologyNational Cheng Kung University Medical CollegeTainan CityTaiwan
  3. 3.Institute of Basic Medical SciencesNational Cheng Kung University Medical CollegeTainan CityTaiwan

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