Editorial to the Special Issue “Electrophysiology”

Wu, Sheng‐Nan; Huang, Chin Wei

doi:10.3390/ijms22062956

Cited by 9 publications

(13 citation statements)

References 10 publications

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“…In accordance with the preceding reports, the V hys phenomenon of I K(M) evoked by the long isosceles-triangular ramp pulse (i.e., the upsloping and downsloping ramp) was revealed in GH 3 cells [73]. The adjustments of such V hys have been recently noticed to serve a role in fine-tuning the activity of ionic channels (e.g., K M channels) to respond when they are virtually needed [62,63,66,73]. We further determined the possible perturbations of SOL on such dynamic and non-equilibrium properties of I K(M) present in GH 3 cells.…”

Section: Discussionsupporting

confidence: 85%

“…In this stage of cell-attached current recordings, we bathed cells in high-K + , Ca 2+ -free solution and the recording electrode used was filled up with low-K + (5.4 mM) solution. As demonstrated in Figure 7, as the examined cell was held at +20 mV relative to the bath, the activity of single-KM channels was robustly detected [51,56,66]. One minute after bath application of SOL, the channel open probability was markedly raised.…”

Section: Stimulatory Effect Of Sol On the Activity Of M-type K + (Km) Channels In Gh3 Cellsmentioning

confidence: 90%

“…The V hys of membrane ionic currents (i.e., a lag in the current amplitude as the linear voltage ramp is changed in the opposite direction) has been recently noticed with an impact on the electrical signal events of varying excitable cells [51,[60][61][62][63][64][65][66]. In other words, V hys behavior is thought to dynamically adjust the voltage sensitivity and kinetics to optimize channel function for appropriately matching its physiological or pathophysiological role in regulation of AP firing [62,63,65].…”

Section: Effect Of Sol On Voltage-dependent Hysteresis (V Hys ) Of I K(m) Activated By Long Isosceles-triangular Ramp Pulsementioning

confidence: 99%

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The Effectiveness in Activating M-Type K+ Current Produced by Solifenacin ([(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate): Independent of Its Antimuscarinic Action

Cho

Chuang

2021

IJMS

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Solifenacin (Vesicare®, SOL), known to be a member of isoquinolines, is a muscarinic antagonist that has anticholinergic effect, and it has been beneficial in treating urinary incontinence and neurogenic detrusor overactivity. However, the information regarding the effects of SOL on membrane ionic currents is largely uncertain, despite its clinically wide use in patients with those disorders. In this study, the whole-cell current recordings revealed that upon membrane depolarization in pituitary GH3 cells, the exposure to SOL concentration-dependently increased the amplitude of M-type K+ current (IK(M)) with effective EC50 value of 0.34 μM. The activation time constant of IK(M) was concurrently shortened in the SOL presence, hence yielding the KD value of 0.55 μM based on minimal reaction scheme. As cells were exposed to SOL, the steady-state activation curve of IK(M) was shifted along the voltage axis to the left with no change in the gating charge of the current. Upon an isosceles-triangular ramp pulse, the hysteretic area of IK(M) was increased by adding SOL. As cells were continually exposed to SOL, further application of acetylcholine (1 μM) failed to modify SOL-stimulated IK(M); however, subsequent addition of thyrotropin releasing hormone (TRH, 1 μM) was able to counteract SOL-induced increase in IK(M) amplitude. In cell-attached single-channel current recordings, bath addition of SOL led to an increase in the activity of M-type K+ (KM) channels with no change in the single channel conductance; the mean open time of the channel became lengthened. In whole-cell current-clamp recordings, the SOL application reduced the firing of action potentials (APs) in GH3 cells; however, either subsequent addition of TRH or linopirdine was able to reverse SOL-mediated decrease in AP firing. In hippocampal mHippoE-14 neurons, the IK(M) was also stimulated by adding SOL. Altogether, findings from this study disclosed for the first time the effectiveness of SOL in interacting with KM channels and hence in stimulating IK(M) in electrically excitable cells, and this noticeable action appears to be independent of its antagonistic activity on the canonical binding to muscarinic receptors expressed in GH3 or mHippoE-14 cells.

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Section: Discussionsupporting

confidence: 85%

Section: Stimulatory Effect Of Sol On the Activity Of M-type K + (Km) Channels In Gh3 Cellsmentioning

confidence: 90%

Section: Effect Of Sol On Voltage-dependent Hysteresis (V Hys ) Of I K(m) Activated By Long Isosceles-triangular Ramp Pulsementioning

confidence: 99%

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The Effectiveness in Activating M-Type K+ Current Produced by Solifenacin ([(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate): Independent of Its Antimuscarinic Action

Cho

Chuang

2021

IJMS

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“…Furthermore, subsequent addition of ivabradine, but still in the continued presence of oxaliplatin, could attenuate oxaliplatin-mediated increase in the ∆area of Hys (V) in response to triangular V ramp [ 11 ]. Ivabradine has been reported to be an inhibitor of I h [ 18 , 28 , 29 , 30 ]. Therefore, the oxaliplatin actions occurring in vivo are not exclusively connected to the formation of platinum-DNA adducts.…”

Section: Hys (V) Behavior Residing In Hyperpolariz...mentioning

confidence: 99%

“…Moreover, with the continued presence of honokiol, the further application oxaliplatin could attenuate honokiol-mediated decrease of the ∆area of the Hys (V) in response to triangular V ramp . Oxaliplatin was previously reported to enhance the Hys (V) strength of I h [ 11 , 12 , 30 ]. However, although the voltage ranges in which I h activation occurs, either in control conditions or after the honokiol treatment, appear to fall outside of the values of the membrane in a neuron, it needs to be noted that a small fraction of I h is tonically activated at rest [ 33 ].…”

Section: Hys (V) Behavior Residing In Hyperpolariz...mentioning

confidence: 99%

Effective Perturbations by Small-Molecule Modulators on Voltage-Dependent Hysteresis of Transmembrane Ionic Currents

Cho

et al. 2022

IJMS

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The non-linear voltage-dependent hysteresis (Hys(V)) of voltage-gated ionic currents can be robustly activated by the isosceles-triangular ramp voltage (Vramp) through digital-to-analog conversion. Perturbations on this Hys(V) behavior play a role in regulating membrane excitability in different excitable cells. A variety of small molecules may influence the strength of Hys(V) in different types of ionic currents elicited by long-lasting triangular Vramp. Pirfenidone, an anti-fibrotic drug, decreased the magnitude of Ih’s Hys(V) activated by triangular Vramp, while dexmedetomidine, an agonist of α2-adrenoceptors, effectively suppressed Ih as well as diminished the Hys(V) strength of Ih. Oxaliplatin, a platinum-based anti-neoplastic drug, was noted to enhance the Ih’s Hys(V) strength, which is thought to be linked to the occurrence of neuropathic pain, while honokiol, a hydroxylated biphenyl compound, decreased Ih’s Hys(V). Cell exposure to lutein, a xanthophyll carotenoid, resulted in a reduction of Ih’s Hys(V) magnitude. Moreover, with cell exposure to UCL-2077, SM-102, isoplumbagin, or plumbagin, the Hys(V) strength of erg-mediated K+ current activated by triangular Vramp was effectively diminished, whereas the presence of either remdesivir or QO-58 respectively decreased or increased Hys(V) magnitude of M-type K+ current. Zingerone, a methoxyphenol, was found to attenuate Hys(V) (with low- and high-threshold loops) of L-type Ca2+ current induced by long-lasting triangular Vramp. The Hys(V) properties of persistent Na+ current (INa(P)) evoked by triangular Vramp were characterized by a figure-of-eight (i.e., ∞) configuration with two distinct loops (i.e., low- and high-threshold loops). The presence of either tefluthrin, a pyrethroid insecticide, or t-butyl hydroperoxide, an oxidant, enhanced the Hys(V) strength of INa(P). However, further addition of dapagliflozin can reverse their augmenting effects in the Hys(V) magnitude of the current. Furthermore, the addition of esaxerenone, mirogabalin, or dapagliflozin was effective in inhibiting the strength of INa(P). Taken together, the observed perturbations by these small-molecule modulators on Hys(V) strength in different types of ionic currents evoked during triangular Vramp are expected to influence the functional activities (e.g., electrical behaviors) of different excitable cells in vitro or in vivo.

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Effective suppression of I and I caused by capsazepine, known to be a blocker of TRPV1 receptor

Wong,

Shih,

Cho

et al. 2024

Brain Research

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Editorial to the Special Issue “Electrophysiology”

Abstract: Ion channels are well recognized to select ions to pass through the cell membrane in a wide variety of cells [...]

Cited by 9 publications

References 10 publications

The Effectiveness in Activating M-Type K+ Current Produced by Solifenacin ([(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate): Independent of Its Antimuscarinic Action

The Effectiveness in Activating M-Type K+ Current Produced by Solifenacin ([(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate): Independent of Its Antimuscarinic Action

Effective Perturbations by Small-Molecule Modulators on Voltage-Dependent Hysteresis of Transmembrane Ionic Currents

Effective suppression of I and I caused by capsazepine, known to be a blocker of TRPV1 receptor

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