Characterization of the Inhibitory Effect of Gastrodigenin and Gastrodin on M-type K+ Currents in Pituitary Cells and Hippocampal Neurons

Yang, Chyun-Yu; Lai, Ming Chi; Liu, Ping Yen; Lo, Yi-Ching; Huang, Chin Wei; Wu, Sheng‐Nan

doi:10.3390/ijms21010117

Cited by 10 publications

(14 citation statements)

References 31 publications

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“…The present observations also revealed that SSM could decrease the amplitude of I K(M) in GH 3 cells with an IC 50 of 4.8 µM. I K(M) is biophysically characterized by a slow activation and deactivation property during step depolarization [34][35][36]. It needs to be noticed, therefore, that the inhibition of I Na caused by SSM or SesA could be indirectly and concurrently altered by their inhibitory effects on I K(M) observed in non-voltage-clamped cells, since the suppression of I Na amplitude would be further exacerbated by the membrane depolarization produced by I K(M) inhibition.…”

Section: Discussionsupporting

confidence: 68%

“…The following experiments were further undertaken to determine whether the addition of SSM could exert any perturbations on the amplitude or gating of I K(M) in these cells [34][35][36]. Cells were bathed in high-K + , Ca 2+ -free solution, and the recording pipette was then filled with K + -enriched solution.…”

Section: Concentration-dependent Inhibition Of M-type K + Currents (Imentioning

confidence: 99%

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Effects of Sesamin, the Major Furofuran Lignan of Sesame Oil, on the Amplitude and Gating of Voltage-Gated Na+ and K+ Currents

et al. 2020

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Sesamin (SSM) and sesamolin (SesA) are the two major furofuran lignans of sesame oil and they have been previously noticed to exert various biological actions. However, their modulatory actions on different types of ionic currents in electrically excitable cells remain largely unresolved. The present experiments were undertaken to explore the possible perturbations of SSM and SesA on different types of ionic currents, e.g., voltage-gated Na+ currents (INa), erg-mediated K+ currents (IK(erg)), M-type K+ currents (IK(M)), delayed-rectifier K+ currents (IK(DR)) and hyperpolarization-activated cation currents (Ih) identified from pituitary tumor (GH3) cells. The exposure to SSM or SesA depressed the transient and late components of INa with different potencies. The IC50 value of SSM needed to lessen the peak or sustained INa was calculated to be 7.2 or 0.6 μM, while that of SesA was 9.8 or 2.5 μM, respectively. The dissociation constant of SSM-perturbed inhibition on INa, based on the first-order reaction scheme, was measured to be 0.93 μM, a value very similar to the IC50 for its depressant action on sustained INa. The addition of SSM was also effective at suppressing the amplitude of resurgent INa. The addition of SSM could concentration-dependently inhibit the IK(M) amplitude with an IC50 value of 4.8 μM. SSM at a concentration of 30 μM could suppress the amplitude of IK(erg), while at 10 μM, it mildly decreased the IK(DR) amplitude. However, the addition of neither SSM (10 μM) nor SesA (10 μM) altered the amplitude or kinetics of Ih in response to long-lasting hyperpolarization. Additionally, in this study, a modified Markovian model designed for SCN8A-encoded (or NaV1.6) channels was implemented to evaluate the plausible modifications of SSM on the gating kinetics of NaV channels. The model demonstrated herein was well suited to predict that the SSM-mediated decrease in peak INa, followed by increased current inactivation, which could largely account for its favorable decrease in the probability of the open-blocked over open state of NaV channels. Collectively, our study provides evidence that highlights the notion that SSM or SesA could block multiple ion currents, such as INa and IK(M), and suggests that these actions are potentially important and may participate in the functional activities of various electrically excitable cells in vivo.

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Section: Discussionsupporting

confidence: 68%

Section: Concentration-dependent Inhibition Of M-type K + Currents (Imentioning

confidence: 99%

Effects of Sesamin, the Major Furofuran Lignan of Sesame Oil, on the Amplitude and Gating of Voltage-Gated Na+ and K+ Currents

et al. 2020

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“…In another separate measurements, we further checked whether the effect of RDV on the amplitude or gating of another type of K + current (i.e., M-type K + current [I K(M) ]) endogenously in GH 3 cells (Sankaranarayanan and Simasko, 1996;Selyanko et al, 1999;Yang et al, 2019). The cells were bathed in high-K + , Ca 2+ -free solution, and the K + -containing solution was used to fill up the recording electrode.…”

Section: Rdv On M-type K + Current (I K(m) ) In Gh 3 Cellsmentioning

confidence: 99%

“…Furthermore, the KCNQ2, KCNQ3, and KCNQ5 genes have been noticed to encode the main subunits of K V 7.2, K V 7.3, and K V 7.5 channels, respectively; and among them, the augmented activity produces the M-type K + current (I K(M) ), which is characterized by a slowly activating and deactivating property (Brown and Adams, 1980;Sankaranarayanan and Simasko, 1996;Wang et al, 1998;Selyanko et al, 1999;Shu et al, 2007;Lu et al, 2019;So et al, 2019;Yang et al, 2019). With growing recognition, targeting I K(M) is regarded as a treatment of various neurologic diseases.…”

Section: Introductionmentioning

confidence: 99%

Evidence for the Effectiveness of Remdesivir (GS-5734), a Nucleoside-Analog Antiviral Drug in the Inhibition of IK(M) or IK(DR) and in the Stimulation of IMEP

et al. 2020

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Remdesivir (RDV, GS-5734), a broad-spectrum antiviral drug in the class of nucleotide analogs, has been particularly tailored for treatment of coronavirus infections. However, to which extent RDV is able to modify various types of membrane ion currents remains largely uncertain. In this study, we hence intended to explore the possible perturbations of RDV on ionic currents endogenous in pituitary GH 3 cells and Jurkat T-lymphocytes. The whole-cell current recordings of ours disclosed that upon membrane depolarization in GH 3 cells the exposure to RDV concentration-dependently depressed the peak or late components of I K(DR) elicitation with effective IC 50 values of 10.1 or 2.8 mM, respectively; meanwhile, the value of dissociation constant of RDV-induced blockage of I K(DR) on the basis of the first-order reaction was yielded to be 3.04 mM. Upon the existence of RDV, the steady-state inactivation curve of I K(DR) was established in the RDV presence; moreover, the recovery became slowed. However, RDV-induced blockage of I K(DR) failed to be overcome by further addition of either a,b-methylene ATP or cyclopentyl-1,3dipropylxanthine. The RDV addition also lessened the strength of M-type K + current with the IC 50 value of 2.5 mM. The magnitude of voltage hysteresis of I K(M) elicited by longlasting triangular ramp pulse was diminished by adding RDV. Membrane electroporationinduced current in response to large hyperpolarization was enhanced, with an EC 50 value of 5.8 mM. Likewise, in Jurkat T-lymphocytes, adding RDV declined I K(DR) amplitude concomitantly with the raised rate of current inactivation applied by step depolarization. Therefore, in terms of the RDV molecule, there appears to be an unintended activity of the prodrug on ion channels. Its inhibition of both I K(DR) and I K(M) occurring in a non-genomic

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“…Gastrodin, a gastrodigenin glycoside, is the main bioactive component of the Gastrodia elata Blume orchid extract used in traditional Chinese medicine. Gastrodin is known to inhibit of the M-type K + currents in neurons with IC 50 19.4 µM ( Yang et al., 2019 ). It has anticonvulsant and analgesic properties alleviating migraine and trigeminal neuralgia, as well demonstrates a neuroprotective effect in ischemia ( Kumar et al., 2013 ; Zeng et al., 2006 ).…”

Section: Natural Ligands Of Acid-sensing Ion Channelsmentioning

confidence: 99%

Animal, Herb, and Microbial Toxins for Structural and Pharmacological Study of Acid-Sensing Ion Channels

Osmakov¹,

Khasanov²,

Andreev³

et al. 2020

Front. Pharmacol.

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Acid-sensing ion channels (ASICs) are of the most sensitive molecular sensors of extracellular pH change in mammals. Six isoforms of these channels are widely represented in membranes of neuronal and non-neuronal cells, where these molecules are involved in different important regulatory functions, such as synaptic plasticity, learning, memory, and nociception, as well as in various pathological states. Structural and functional studies of both wild-type and mutant ASICs are essential for human care and medicine for the efficient treatment of socially significant diseases and ensure a comfortable standard of life. Ligands of ASICs serve as indispensable tools for these studies. Such bioactive compounds can be synthesized artificially. However, to date, the search for such molecules has been most effective amongst natural sources, such as animal venoms or plants and microbial extracts. In this review, we provide a detailed and comprehensive structural and functional description of natural compounds acting on ASICs, as well as the latest information on structural aspects of their interaction with the channels. Many of the examples provided in the review demonstrate the undoubted fundamental and practical successes of using natural toxins. Without toxins, it would not be possible to obtain data on the mechanisms of ASICs’ functioning, provide detailed study of their pharmacological properties, or assess the contribution of the channels to development of different pathologies. The selectivity to different isoforms and variety in the channel modulation mode allow for the appraisal of prospective candidates for the development of new drugs.

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Characterization of the Inhibitory Effect of Gastrodigenin and Gastrodin on M-type K+ Currents in Pituitary Cells and Hippocampal Neurons

Cited by 10 publications

References 31 publications

Effects of Sesamin, the Major Furofuran Lignan of Sesame Oil, on the Amplitude and Gating of Voltage-Gated Na+ and K+ Currents

Effects of Sesamin, the Major Furofuran Lignan of Sesame Oil, on the Amplitude and Gating of Voltage-Gated Na+ and K+ Currents

Evidence for the Effectiveness of Remdesivir (GS-5734), a Nucleoside-Analog Antiviral Drug in the Inhibition of IK(M) or IK(DR) and in the Stimulation of IMEP

Animal, Herb, and Microbial Toxins for Structural and Pharmacological Study of Acid-Sensing Ion Channels

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