TY - JOUR
T1 - Evidence for effective inhibitory actions on hyperpolarization-activated cation current caused by ganoderma triterpenoids, the main active constitutents of ganoderma spores
AU - Chang, Wei Ting
AU - Gao, Zi Han
AU - Lo, Yi Ching
AU - Wu, Sheng Nan
N1 - Funding Information:
Acknowledgments: The authors would like to thank Kaisen Lee and Shih-Wei Li for contributing to part of the earlier experiments. Z.-H. Gao received a student fellowship from Ministry of Science and Technology, Taiwan, while S.-N. Wu received a Talent Award for the Outstanding Researchers from Ministry of Education, Taiwan.
Funding Information:
Funding: The research detailed in this paper is supported in part by grants awarded to S.-N. Wu which were provided both by National Cheng Kung University (D106-35A13, D107-F2519, D108-F2507 and NCKUH-10709001) from Ministry of Education, Taiwan, and by Ministry of Science and Technology (MOST-108-2314-B-006-094), Taiwan.
Publisher Copyright:
© 2019 by the authors.
PY - 2019/11/22
Y1 - 2019/11/22
N2 - The triterpenoid fraction of Ganoderma (Ganoderma triterpenoids, GTs) has been increasingly demonstrated to provide effective antioxidant, neuroprotective or cardioprotective activities. However, whether GTs is capable of perturbing the transmembrane ionic currents existing in electrically excitable cells is not thoroughly investigated. In this study, an attempt was made to study whether GTs could modify hyperpolarization-activated cation currents (Ih) in pituitary tumor (GH3) cells and in HL-1 atrial cardiomyocytes. In whole-cell current recordings, the addition of GTs produced a dose-dependent reduction in the amplitude of Ih in GH3 cells with an IC50 value of 11.7 μg/mL, in combination with a lengthening in activation time constant of the current. GTs (10 μg/mL) also caused a conceivable shift in the steady-state activation curve of Ih along the voltage axis to a more negative potential by approximately 11 mV. Subsequent addition of neither 8-cyclopentyl-1,3-dipropylxanthine nor 8-(p-sulfophenyl)theophylline, still in the presence of GTs, could attenuate GTs-mediated inhibition of Ih. In current-clamp voltage recordings, GTs diminished the firing frequency of spontaneous action potentials in GH3 cells, and it also decreased the amplitude of sag potential in response to hyperpolarizing current stimuli. In murine HL-1 cardiomyocytes, the GTs addition also suppressed the amplitude of Ih effectively. In DPCPX (1 μM)-treated HL-1 cells, the inhibitory effect of GTs on Ih remained efficacious. Collectively, the inhibition of Ih caused by GTs is independent of its possible binding to adenosine receptors and it might have profound influence in electrical behaviors of different types of electrically excitable cells (e.g., pituitary and heart cells) if similar in vitro or in vivo findings occur.
AB - The triterpenoid fraction of Ganoderma (Ganoderma triterpenoids, GTs) has been increasingly demonstrated to provide effective antioxidant, neuroprotective or cardioprotective activities. However, whether GTs is capable of perturbing the transmembrane ionic currents existing in electrically excitable cells is not thoroughly investigated. In this study, an attempt was made to study whether GTs could modify hyperpolarization-activated cation currents (Ih) in pituitary tumor (GH3) cells and in HL-1 atrial cardiomyocytes. In whole-cell current recordings, the addition of GTs produced a dose-dependent reduction in the amplitude of Ih in GH3 cells with an IC50 value of 11.7 μg/mL, in combination with a lengthening in activation time constant of the current. GTs (10 μg/mL) also caused a conceivable shift in the steady-state activation curve of Ih along the voltage axis to a more negative potential by approximately 11 mV. Subsequent addition of neither 8-cyclopentyl-1,3-dipropylxanthine nor 8-(p-sulfophenyl)theophylline, still in the presence of GTs, could attenuate GTs-mediated inhibition of Ih. In current-clamp voltage recordings, GTs diminished the firing frequency of spontaneous action potentials in GH3 cells, and it also decreased the amplitude of sag potential in response to hyperpolarizing current stimuli. In murine HL-1 cardiomyocytes, the GTs addition also suppressed the amplitude of Ih effectively. In DPCPX (1 μM)-treated HL-1 cells, the inhibitory effect of GTs on Ih remained efficacious. Collectively, the inhibition of Ih caused by GTs is independent of its possible binding to adenosine receptors and it might have profound influence in electrical behaviors of different types of electrically excitable cells (e.g., pituitary and heart cells) if similar in vitro or in vivo findings occur.
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U2 - 10.3390/molecules24234256
DO - 10.3390/molecules24234256
M3 - Article
C2 - 31766737
AN - SCOPUS:85075581869
SN - 1420-3049
VL - 24
JO - Molecules
JF - Molecules
IS - 23
M1 - 4256
ER -