The calmodulin inhibitor CGS 9343B inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

Li, Hongliang; Hong, Da Hye; Kim, Han Sol; Kim, Hye Won; Jung, Won‐Kyo; Na, Sung Hun; Jung, In Duk; Park, Yeong‐Min; Choi, Il‐Whan; Park, Won Sun

doi:10.1016/j.taap.2015.03.012

Cited by 14 publications

(4 citation statements)

References 33 publications

(35 reference statements)

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“…In addition, Ca 2+ channel inhibitors, including verapamil, mibefradil, efonidipine, and NNC 55‐0396, directly inhibit vascular Kv channels independent of Ca 2+ channel inhibition . Calmodulin inhibitors, such as trifluoperazine, W‐7, and CGS 9343B, have also been reported to inhibit the vascular Kv current irrespective of calmodulin inhibition . Our group recently revealed that another SSRI, fluvoxamine, inhibits vascular Kv channels independent of serotonin reuptake inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23][24] Calmodulin inhibitors, such as trifluoperazine, W-7, and CGS 9343B, have also been reported to inhibit the vascular Kv current irrespective of calmodulin inhibition. [25][26][27] Our group recently revealed that another SSRI, fluvoxamine, inhibits vascular Kv channels independent of serotonin reuptake inhibition. Similar to the results obtained using dapoxetine, fluvoxamine shifted the inactivation curves toward a negative potential without altering the activation curves.…”

Section: Discussionmentioning

confidence: 99%

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The selective serotonin reuptake inhibitor dapoxetine inhibits voltage‐dependent K⁺ channels in rabbit coronary arterial smooth muscle cells

Kim

et al. 2017

Clin Exp Pharma Physio

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We investigated the inhibitory effect of dapoxetine, a selective serotonin reuptake inhibitor (SSRI), on voltage-dependent K (Kv) channels using native smooth muscle cells from rabbit coronary arteries. Dapoxetine inhibited Kv channel currents in a concentration-dependent manner, with an IC value of 2.68±0.94 μmol/L and a slope value (Hill coefficient) of 0.63±0.11. Application of 10 μmol/L dapoxetine accelerated the rate of inactivation of Kv currents. Although dapoxetine did not modify current activation kinetics, it caused a significant negative shift in the inactivation curves. Application of train step (1 or 2 Hz) progressively increased the inhibitory effect of dapoxetine on Kv channels. In addition, the recovery time constant was extended in its presence, suggesting that the longer recovery time constant from inactivation underlies a use-dependent inhibition of the channel. From these results, we conclude that dapoxetine inhibits Kv channels in a dose-, time-, use-, and state (open)-dependent manner, independent of serotonin reuptake inhibition.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The selective serotonin reuptake inhibitor dapoxetine inhibits voltage‐dependent K⁺ channels in rabbit coronary arterial smooth muscle cells

Kim

et al. 2017

Clin Exp Pharma Physio

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“…Many drugs and other chemicals exert side effects on Kv channels independently of their original targets. For example, calmodulin inhibitors such as trifluoperazine, W-7, and CGS 9343B, inhibit the vascular Kv current independently of calmodulin inhibition [26][27][28] . In addition, the Ca 2+ channel inhibitors NNC 55-0396, verapamil, efonidipine, and mibefradil directly inhibit Kv channels in rabbit coronary arterial smooth muscle cells [29][30][31][32] .…”

Section: Effect Of Another Rock Inhibitor On the Inhibition Of Kv Chamentioning

confidence: 99%

Y-27632, a Rho-Associated Protein Kinase Inhibitor, Inhibits Voltage-Dependent K+ Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Shin²,

Kim³

et al. 2016

Pharmacology

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We examined the effects of the Rho-associated protein kinase (ROCK) inhibitor Y-27632 on voltage-dependent K⁺ (Kv) channels in rabbit coronary arterial smooth muscle cells using the whole-cell patch clamp technique. Y-27632 reduced the amplitude of the Kv current in a concentration-dependent manner, with an IC₅₀ of 0.87 ± 0.06 μmol/l and a Hill coefficient of 1.48 ± 0.06. Y-27632 did not affect the steady-state activation or inactivation curves, suggesting that the drug does not affect the voltage sensitivity of Kv channels. Another ROCK inhibitor, H-1152, did not affect the Kv current and had no significant effect on the Y-27632-induced inhibition of Kv channels, indicating that the inhibitory effect of Y-27632 on the Kv current is independent of ROCK signaling. From these results, we conclude that Y-27632 inhibits the Kv channel current in a dose-dependent and ROCK signaling-independent manner.

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“…Previous studies have demonstrated that four types of K + channel are expressed in vascular smooth muscle: voltage‐dependent K + (Kv), inwardly rectifying K + (Kir), large‐conductance Ca 2+ ‐activated K + (BK Ca ), and K ATP channels . Although most of the K + channels are at least partially involved in maintaining vascular tone, Kv channels are regarded as one of the most crucial channels in determining the resting membrane potential and thereby the basal tone of the vessel . Kv channels are also strongly regulated by intracellular protein kinases including protein kinase C (PKC), protein kinase A (PKA), and protein kinase G (PKG), which are associated with numerous cellular functions .…”

Section: Introductionmentioning

confidence: 99%

The vasorelaxant effect of antidiabetic drug nateglinide via activation of voltage‐dependent K⁺ channels in aortic smooth muscle

Kim

Shin

et al. 2017

Cardiovascular Therapeutics

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Summary Aims We investigated the vasorelaxant effect of nateglinide and its related mechanisms using phenylephrine (Phe)‐induced precontracted aortic rings. Methods Arterial tone measurement was performed in aortic smooth muscle. Results The application of nateglinide induced vasorelaxation in a concentration‐dependent manner. Pretreatment with the large‐conductance Ca2+‐activated K+ (BKCa) channel inhibitor paxilline, the inwardly rectifying K+ (Kir) channel inhibitor Ba2+, and ATP‐sensitive K+ (KATP) channel inhibitor glibenclamide did not affect the vasorelaxant effect of nateglinide. However, pretreatment with the voltage‐dependent K+ (Kv) channel inhibitor 4‐aminopyridine (4‐AP) effectively reduced the vasorelaxant effect of nateglinide. Pretreatment with the Ca2+ inhibitor nifedipine and the sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase inhibitor thapsigargin did not change the vasorelaxant effect of nateglinide. Additionally, the vasorelaxant effect of nateglinide was not altered in the presence of an adenylyl cyclase, a protein kinase A, a guanylyl cyclase, or a protein kinase G inhibitor. The vasorelaxant effect of nateglinide was not affected by the elimination of the endothelium. In addition, pretreatment with a nitric oxide synthase inhibitor, L‐NAME, and a small‐conductance Ca2+‐activated K+ (SKCa) channel inhibitor, apamin, did not change the vasorelaxant effect of nateglinide. Conclusion Nateglinide induced vasorelaxation via the activation of the Kv channel independent of other K+ channels, Ca2+ channels, intracellular Ca2+ ([Ca2+]i), and the endothelium.

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The calmodulin inhibitor CGS 9343B inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

Cited by 14 publications

References 33 publications

The selective serotonin reuptake inhibitor dapoxetine inhibits voltage‐dependent K⁺ channels in rabbit coronary arterial smooth muscle cells

The selective serotonin reuptake inhibitor dapoxetine inhibits voltage‐dependent K⁺ channels in rabbit coronary arterial smooth muscle cells

Y-27632, a Rho-Associated Protein Kinase Inhibitor, Inhibits Voltage-Dependent K+ Channels in Rabbit Coronary Arterial Smooth Muscle Cells

The vasorelaxant effect of antidiabetic drug nateglinide via activation of voltage‐dependent K⁺ channels in aortic smooth muscle

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The calmodulin inhibitor CGS 9343B inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

Cited by 14 publications

References 33 publications

The selective serotonin reuptake inhibitor dapoxetine inhibits voltage‐dependent K+ channels in rabbit coronary arterial smooth muscle cells

The selective serotonin reuptake inhibitor dapoxetine inhibits voltage‐dependent K+ channels in rabbit coronary arterial smooth muscle cells

Y-27632, a Rho-Associated Protein Kinase Inhibitor, Inhibits Voltage-Dependent K+ Channels in Rabbit Coronary Arterial Smooth Muscle Cells

The vasorelaxant effect of antidiabetic drug nateglinide via activation of voltage‐dependent K+ channels in aortic smooth muscle

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The selective serotonin reuptake inhibitor dapoxetine inhibits voltage‐dependent K⁺ channels in rabbit coronary arterial smooth muscle cells

The selective serotonin reuptake inhibitor dapoxetine inhibits voltage‐dependent K⁺ channels in rabbit coronary arterial smooth muscle cells

The vasorelaxant effect of antidiabetic drug nateglinide via activation of voltage‐dependent K⁺ channels in aortic smooth muscle