| Summary: | The triterpenoid fraction of <i>Ganoderma</i> (<i>Ganoderma</i> 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 (<i>I</i><sub>h</sub>) in pituitary tumor (GH<sub>3</sub>) 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 <i>I</i><sub>h</sub> in GH<sub>3</sub> cells with an IC<sub>50</sub> 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 <i>I</i><sub>h</sub> along the voltage axis to a more negative potential by approximately 11 mV. Subsequent addition of neither 8-cyclopentyl-1,3-dipropylxanthine nor 8-(<i>p</i>-sulfophenyl)theophylline, still in the presence of GTs, could attenuate GTs-mediated inhibition of <i>I</i><sub>h</sub>. In current-clamp voltage recordings, GTs diminished the firing frequency of spontaneous action potentials in GH<sub>3</sub> 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 <i>I</i><sub>h</sub> effectively. In DPCPX (1 µM)-treated HL-1 cells, the inhibitory effect of GTs on <i>I</i><sub>h</sub> remained efficacious. Collectively, the inhibition of <i>I</i><sub>h</sub> 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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