TY - JOUR
T1 - Enhanced β-adrenergic response in mice with dominant-negative expression of the PKD2L1 channel
AU - Murakami, Manabu
AU - Murakami, Agnieszka M.
AU - Nemoto, Takayuki
AU - Ohba, Takayoshi
AU - Yonekura, Manabu
AU - Toyama, Yuichi
AU - Tomita, Hirofumi
AU - Matsuzaki, Yasushi
AU - Sawamura, Daisuke
AU - Hirota, Kazuyoshi
AU - Itagaki, Shirou
AU - Asada, Yujiro
AU - Miyoshi, Ichiro
N1 - Publisher Copyright:
© 2022 Murakami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/1
Y1 - 2022/1
N2 - Polycystic kidney disease (PKD) is the most common genetic cause of kidney failure in humans. Among the various PKD-related molecules, PKD2L1 forms cation channels, but its physiological importance is obscure. In the present study, we established a transgenic mouse line by overexpressing the dominant-negative form of the mouse PKD2L1 gene (i.e., lacking the pore-forming domain). The resulting PKD2L1del-Tg mice exhibited supraventricular premature contraction, as well as enhanced sensitivity to β-adrenergic stimulation and unstable R-R intervals in electrocardiography. During spontaneous atrial contraction, PKD2L1del-Tg atria showed enhanced sensitivity to isoproterenol, norepinephrine, and epinephrine. Action potential recording revealed a shortened action potential duration in PKD2L1del-Tg atria in response to isoproterenol. These findings indicated increased adrenergic sensitivity in PKD2L1del-Tg mice, suggesting that PKD2L1 is involved in sympathetic regulation.
AB - Polycystic kidney disease (PKD) is the most common genetic cause of kidney failure in humans. Among the various PKD-related molecules, PKD2L1 forms cation channels, but its physiological importance is obscure. In the present study, we established a transgenic mouse line by overexpressing the dominant-negative form of the mouse PKD2L1 gene (i.e., lacking the pore-forming domain). The resulting PKD2L1del-Tg mice exhibited supraventricular premature contraction, as well as enhanced sensitivity to β-adrenergic stimulation and unstable R-R intervals in electrocardiography. During spontaneous atrial contraction, PKD2L1del-Tg atria showed enhanced sensitivity to isoproterenol, norepinephrine, and epinephrine. Action potential recording revealed a shortened action potential duration in PKD2L1del-Tg atria in response to isoproterenol. These findings indicated increased adrenergic sensitivity in PKD2L1del-Tg mice, suggesting that PKD2L1 is involved in sympathetic regulation.
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U2 - 10.1371/journal.pone.0261668
DO - 10.1371/journal.pone.0261668
M3 - Article
C2 - 35051185
AN - SCOPUS:85123294257
SN - 1932-6203
VL - 17
JO - PLoS One
JF - PLoS One
IS - 1 January
M1 - e0261668
ER -