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Inhibitory effect of oestradiol on the cardiac KV7.1/KCNE1 channel is species dependent

Veronika A Linhart1, Lucas Dauga1, Sara I Liin1

  • 1Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Experimental Physiology
|May 5, 2025
PubMed

Insights

Oestradiol (17β-E2) affects cardiac KV7.1/KCNE1 channels, prolonging action potential duration. This study reveals species-specific responses in guinea pig, rabbit, and zebrafish KV7.1/KCNE1 channels to 17β-E2, impacting cardiac electrophysiology research.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Pharmacology
  • Ion Channel Biology

Background:

  • Oestradiol (17β-E2) influences cardiac action potential duration and QT interval by modulating cardiac ion channels.
  • Previous research indicates 17β-E2 inhibits the KV7.1/KCNE1 channel, but findings show variability in effects and effective concentrations.
  • Species-specific differences in KV7.1/KCNE1 channel pharmacology may explain observed variability in 17β-E2 effects.

Purpose of the Study:

  • To investigate whether species-specific pharmacological profiles of KV7.1/KCNE1 channels contribute to variability in 17β-E2 effects.
  • To quantitatively compare the effects of 17β-E2 on KV7.1/KCNE1 channels from guinea pig, zebrafish, and rabbit.

Main Methods:

  • Utilized the two-electrode voltage clamp technique.
  • Expressed KV7.1/KCNE1 channels from guinea pig, zebrafish, and rabbit in Xenopus oocytes.
  • Characterized and compared the inhibitory effects of 17β-E2 on channel activity across species.

Main Results:

  • KV7.1/KCNE1 channels from all tested species (guinea pig, rabbit, zebrafish) were inhibited by 17β-E2.
  • Observed species-specific variability in 17β-E2 response: guinea pig channels responded similarly to human, rabbit channels were sensitive to lower concentrations, and zebrafish channels showed altered voltage dependence.
  • Determined that species variability arises from the KV7.1/KCNE1 complex, not individual subunits.

Conclusions:

  • Species variability in KV7.1/KCNE1 channel response to 17β-E2 is confirmed.
  • These findings highlight the importance of considering species-specific channel behavior when selecting animal models for cardiovascular research.
  • Understanding these differences is crucial for accurate interpretation of experimental results involving 17β-E2 and cardiac ion channels.
Keywords:
KCNQ1electrophysiologyhormone

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