Protein tyrosine kinase-dependent modulation of voltage-dependent potassium channels by genistein in rat cardiac ventricular myocytes

Gao, Zhan; Lau, Chi-Wai; Wong, Tung Po; Li, Gui-Rong

doi:10.1016/j.cellsig.2003.08.003

Cited by 36 publications

(32 citation statements)

References 25 publications

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“…The inactivation kinetics of Kv1.4 were slowed in the subthreshold range of depolarization, but remained unchanged at depolarizing potentials (43). Genistein produced no significant voltage-dependent changes of transient outward K ϩ current activation or inactivation (12,38). In the present study, genistein affected neither the activation nor the inactivation kinetics of Kv4.3, but it shifted the steady-state inactivation curves in a hyperpolarizing direction.…”

Section: Discussioncontrasting

confidence: 62%

“…Using genistein, the PTKdependent pathway was shown to be involved in the suppression of both the slow delayed-rectifier K ϩ current in guinea pig ventricular myocytes and the voltage-gated K ϩ channels expressed in Xenopus oocytes and human embryonic kidney cells (17,26). Moreover, transient outward K ϩ currents were inhibited by genistein via PTK-dependent mechanisms in human atrial and rat ventricular myocytes (12,28,38). Additional studies show that genistein markedly reduced the amplitude of a slowly inactivating delayed rectifier current and, to a lesser extent, that of a transient K ϩ current in mouse Schwann cells (31).…”

mentioning

confidence: 99%

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Inhibition of Kv4.3 by genistein via a tyrosine phosphorylation-independent mechanism

Kim

Ahn

Choi

et al. 2011

American Journal of Physiology-Cell Physiology

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Section: Discussioncontrasting

confidence: 62%

mentioning

confidence: 99%

Inhibition of Kv4.3 by genistein via a tyrosine phosphorylation-independent mechanism

Kim

Ahn

Choi

et al. 2011

American Journal of Physiology-Cell Physiology

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“…Hence, we addressed the possibility that diamide-induced electrophysiological changes were indirectly mediated by activation of kinase pathways, some of which acutely regulate K + currents in ventricular myocytes [24,25,27]. In our studies, neither calphostin C nor GF109203x affected the ability of diamide to inhibit I peak or I ss , indicating that PKC activation was not involved.…”

Section: Differential Control Of K + Currents By Thioredoxin and Glutmentioning

confidence: 91%

“…Although not studied as extensively as PKC, it is also known that activation of other kinase pathways, such as tyrosine kinase, can modulate K + channels in heart [27]. Thus, to determine if K + current inhibition by diamide was mediated by a phosphorylase mechanism, a first series of experiments was done where cells were pretreated with the pan-specific PKC inhibitors calphostin C (100 nmol/l) or GF109203x (50 nmol/ l) for 30 min before adding diamide for 20 min.…”

Section: Mediators Of K + Current Inhibitionmentioning

confidence: 99%

“…Studies in various cell types suggest that protein tyrosine kinase can modulate Kv channels, although the net effect of kinase activation is unclear. For example, genistein has been shown to inhibit I to in rat ventricular [27] and human atrial [44] myocytes. In expressed Shaker channels (Kv1.5, Kv1.4), Src tyrosine kinase binds to the α-subunit and inhibits macroscopic currents [45,46], although rat Kv1.5 does not co-immunoprecipitate with Src as does the human isoform [46].…”

Section: Differential Control Of K + Currents By Thioredoxin and Glutmentioning

confidence: 99%

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Oxidoreductase regulation of Kv currents in rat ventricle

Liang

et al. 2008

Journal of Molecular and Cellular Cardiology

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Oxidative stress contributes to the arrhythmogenic substrate created by myocardial ischemiareperfusion partly through a shift in cell redox state, a key modulator of protein function. The activity of many oxidation-sensitive proteins is controlled by oxidoreductase systems that regulate the redox state of cysteine thiol groups, but the impact of these systems on ion channel function is not well defined. Thus, we examined the roles of the thioredoxin and glutaredoxin systems in controlling K + channels in the ventricle. An oxidative shift in redox state was elicited in isolated rat ventricular myocytes by brief exposure to diamide, a thiol-specific, membrane-permeable oxidant. Voltageclamp studies showed that diamide decreased peak outward K + current (I peak ) evoked by depolarizing test pulses by 41% (+60 mV; p<0.05) while steady-state outward current (I ss ) measured at the end of the test pulse was decreased by 45% (p<0.05). These electrophysiological effects were not prevented by protein kinase C blockers, but the tyrosine kinase inhibitors genistein or lavendustin A blocked the suppression of both K + currents by diamide. Moreover, inhibition of I peak and I ss by diamide was reversed by dichloroacetate and an insulin-mimetic. The effect of dichloroacetate to normalize I peak after diamide was blocked by the thioredoxin system inhibitors auranofin or 13-cisretinoic acid, but I ss was not affected by either compound. A pan-specific inhibitor of glutaredoxin and thioredoxin systems, 1,3-bis-(2-chloroethyl)-1-nitrosourea, also blocked the dichloroacetate effect on I peak but only partially inhibited the recovery of I ss . These data suggest that acute regulation of cardiac K + channels by oxidoreductase systems is mediated by redox-sensitive tyrosine kinase/ phosphatase pathways. The pathways controlling I peak channels are targets of the thioredoxin system whereas those regulating I ss channels are likely controlled by the glutaredoxin system. Thus, cardiac oxidoreductase systems may be important regulators of ion channels affected by pathogenic oxidative stress.

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Mg²⁺‐Dependent Modulation of BK_Ca Channels by Genistein in Rat Arteriolar Smooth Muscle Cells

Wang

Zhao

Zhou

et al. 2014

Journal Cellular Physiology

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Genistein, a protein tyrosine kinase (PTK) inhibitor, regulates ion channel activities. However, the mechanism of action of genistein on large-conductance calcium-activated potassium (BK(Ca)) channels is unclear. This study aimed to investigate whether the mechanism of Mg(2+)-dependent modulation of BK(Ca) channel activity in vascular smooth muscle cells involved inhibition of phosphorylation by genistein or direct interaction between genistein and BK(Ca) channels. The whole-cell and inside-out patch-clamp techniques were used to measure BK(Ca) currents and the effects of genistein on BK(Ca) channel activities in rat mesenteric arteriolar smooth muscle cells. We found that the effects of genistein on BK(Ca) currents were Mg(2+)-dependent. Genistein (50 μM) inhibited BK(Ca) currents if the intracellular free magnesium concentration ([Mg(2+)]i) was 2 μM or 20 μM, but amplified BK(Ca) currents if [Mg(2+)]i was 200 μM or 2000 μM. The inhibitory effect of genistein on BK(Ca) currents was reversed by the protein tyrosine phosphatase inhibitor sodium orthovanadate (0.5 mM). Daidzein (50 μM), an inactive analogue of genistein, also amplified BK(Ca) currents, and its amplification was insensitive to orthovanadate. Another PTK inhibitor, tyrphostin 23 (50 μM), reduced the open probability of BK(Ca) channels. This inhibitory effect was weaker at 200 μM [Mg(2+)]i than at 2 μM [Mg(2+) ]i, and was countered by orthovanadate. Our results suggest that genistein amplifies BK(Ca) currents at a high [Mg(2+)]i, but inhibits BK(Ca) currents at a low [Mg(2+)]i. The mechanism of this biphasic effects involves PTK-independent amplification and [Mg(2+)]i -PTK-dependent inhibition.

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Protein tyrosine kinase-dependent modulation of voltage-dependent potassium channels by genistein in rat cardiac ventricular myocytes

Cited by 36 publications

References 25 publications

Inhibition of Kv4.3 by genistein via a tyrosine phosphorylation-independent mechanism

Inhibition of Kv4.3 by genistein via a tyrosine phosphorylation-independent mechanism

Oxidoreductase regulation of Kv currents in rat ventricle

Mg²⁺‐Dependent Modulation of BK_Ca Channels by Genistein in Rat Arteriolar Smooth Muscle Cells

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Protein tyrosine kinase-dependent modulation of voltage-dependent potassium channels by genistein in rat cardiac ventricular myocytes

Cited by 36 publications

References 25 publications

Inhibition of Kv4.3 by genistein via a tyrosine phosphorylation-independent mechanism

Inhibition of Kv4.3 by genistein via a tyrosine phosphorylation-independent mechanism

Oxidoreductase regulation of Kv currents in rat ventricle

Mg2+‐Dependent Modulation of BKCa Channels by Genistein in Rat Arteriolar Smooth Muscle Cells

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Mg²⁺‐Dependent Modulation of BK_Ca Channels by Genistein in Rat Arteriolar Smooth Muscle Cells