Abstract
Background: Honokiol (HNK), a dimer of allylphenol obtained from the bark of Magnolia officinalis was demonstrated to exert an array of biological actions in different excitable cell types. However, whether or how this compound can lead to any perturbations on surface–membrane ionic currents remains largely unknown. Methods: We used the patch clamp method and found that addition of HNK effectively depressed the density of macroscopic hyperpolarization-activated cation currents (Ih) in pituitary GH3 cells in a concentration-, time- and voltage-dependent manner. By the use of a two-step voltage protocol, the presence of HNK (10 μM) shifted the steady-state activation curve of Ih density along the voltage axis to a more negative potential by approximately 11 mV, together with no noteworthy modification in the gating charge of the current. Results: The voltage-dependent hysteresis of Ih density elicited by long-lasting triangular ramp pulse was attenuated by the presence of HNK. The HNK addition also diminished the magnitude of deactivating Ih density elicited by ramp-up depolarization with varying durations. The effective half-maximal concentration (IC50) value needed to inhibit the density of Ih or delayed rectifier K+ current identified in GH3 cells was estimated to be 2.1 or 6.8 μM, respectively. In cell-attached current recordings, HNK decreased the frequency of spontaneous action currents. In Rolf B1.T olfactory sensory neurons, HNK was also observed to decrease Ih density in a concentration-dependent manner. Conclusions: The present study highlights the evidence revealing that HNK has the propensity to perturb these ionic currents and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is proposed to be a potential target for the in vivo actions of HNK and its structurally similar compounds.
Highlights
Honokiol (HNK), a hydroxylated biphenyl compound obtained from Magnolia officinalis and from other species of the family Magnoliaceae, has been used in traditional Asian medicines (Houpo, Hou p’u, or Saiboku-tu(o)) [1]
As cells were bathed in Ca2+-free Tyrode’s solution, the applied long-lasting step hyperpolarization was noted to induce an inwardly directed current with the slowly activating and deactivating properties, which has been previously recognized as the hyperpolarization-activated cation current, namely, Ih or funny current (If) (Figure 1A,B) [25,26,30,35,41,42,43]
Within 1 min of exposing the GH3 cell to HNK (3 or 10 μM), the Ih density responding to such membrane hyperpolarization was robustly reduced
Summary
Honokiol (HNK), a hydroxylated biphenyl compound obtained from Magnolia officinalis and from other species of the family Magnoliaceae, has been used in traditional Asian medicines (Houpo, Hou p’u, or Saiboku-tu(o)) [1]. HNK is recognized to be a potential natural compound that has been demonstrated to exert multiple effects on different cellular processes in various cancer models [2,3,4,5,6]. Honokiol (HNK), a dimer of allylphenol obtained from the bark of Magnolia officinalis was demonstrated to exert an array of biological actions in different excitable cell types. Methods: We used the patch clamp method and found that addition of HNK effectively depressed the density of macroscopic hyperpolarization-activated cation currents (Ih) in pituitary GH3 cells in a concentration-, time- and voltage-dependent manner. Conclusions: The present study highlights the evidence revealing that HNK has the propensity to perturb these ionic currents and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is proposed to be a potential target for the in vivo actions of HNK and its structurally similar compounds
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