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Updated: Oct 6, 2025

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
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Enhanced β-adrenergic response in mice with dominant-negative expression of the PKD2L1 channel

Manabu Murakami1, Agnieszka M Murakami2, Takayuki Nemoto1

  • 1Department of Pharmacology, Faculty of Medicine, University of Miyazaki, Miyazaki, Miyazaki, Japan.

Plos One
|January 20, 2022
PubMed

Insights

Polycystic kidney disease (PKD) protein PKD2L1 influences heart function. Overexpressing a dominant-negative PKD2L1 in mice increased their sensitivity to adrenergic stimulation, impacting heart rhythm.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Biology
  • Genetics

Background:

  • Polycystic kidney disease (PKD) is a leading genetic cause of kidney failure.
  • PKD2L1, a PKD-related molecule, forms cation channels, but its physiological role remains unclear.
  • Understanding PKD2L1's function is crucial for PKD research.

Purpose of the Study:

  • To investigate the physiological role of PKD2L1 in cardiac function.
  • To determine the impact of dominant-negative PKD2L1 overexpression on adrenergic sensitivity and heart rhythm.

Main Methods:

  • Generation of a transgenic mouse model overexpressing a dominant-negative PKD2L1 (PKD2L1del-Tg).
  • Electrocardiography to assess heart rhythm and supraventricular premature contractions.
  • Pharmacological challenge with adrenergic agonists (isoproterenol, norepinephrine, epinephrine) to evaluate cardiac response.
  • Action potential recordings in atrial tissue.

Main Results:

  • PKD2L1del-Tg mice displayed supraventricular premature contractions and unstable R-R intervals.
  • Atria from PKD2L1del-Tg mice showed heightened sensitivity to adrenergic stimulation.
  • Isoproterenol challenge resulted in a shortened action potential duration in PKD2L1del-Tg atria.

Conclusions:

  • Overexpression of dominant-negative PKD2L1 leads to increased adrenergic sensitivity in the heart.
  • These findings suggest a role for PKD2L1 in sympathetic regulation of cardiac function.
  • PKD2L1 may be a potential target for modulating cardiac adrenergic responses.

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