Ketamine attenuates the Na+-dependent Ca2+ overload in rabbit ventricular myocytes in vitro by inhibiting late Na+ and L-type Ca2+ currents

Luo, Antao; Cao, Zhijun; Yu, Xiang; Zhang, Shuo; Qian, Chunping; Fu, Chen; Zhang, Peihua; Ma, Jing

doi:10.1038/aps.2015.75

Cited by 12 publications

(10 citation statements)

References 49 publications

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“…In our previous study, we have found that increases in I Na.L contribute to the development of intracellular Ca 2+ overload by enhancing I NCX [25,38] . Another study has demonstrated that elevated [Ca 2+ ] i activates the CaMK II and PKC pathways, and ultimately increases I Na.L and results in the formation of a vicious cycle [39] .…”

Section: Discussionmentioning

confidence: 99%

Barbaloin inhibits ventricular arrhythmias in rabbits by modulating voltage-gated ion channels

et al. 2017

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Barbaloin (10-β-D-glucopyranosyl-1,8-dihydroxy-3-(hydroxymethyl)-9(10H)-anthracenone) is extracted from the aloe plant and has been reported to have anti-inflammatory, antitumor, antibacterial, and other biological activities. Here, we investigated the effects of barbaloin on cardiac electrophysiology, which has not been reported thus far. Cardiac action potentials (APs) and ionic currents were recorded in isolated rabbit ventricular myocytes using whole-cell patch-clamp technique. Additionally, the antiarrhythmic effect of barbaloin was examined in Langendorff-perfused rabbit hearts. In current-clamp recording, application of barbaloin (100 and 200 μmol/L) dose-dependently reduced the action potential duration (APD) and the maximum depolarization velocity (Vmax), and attenuated APD reverse-rate dependence (RRD) in ventricular myocytes. Furthermore, barbaloin (100 and 200 μmol/L) effectively eliminated ATX II-induced early afterdepolarizations (EADs) and Ca-induced delayed afterdepolarizations (DADs) in ventricular myocytes. In voltage-clamp recording, barbaloin (10-200 μmol/L) dose-dependently inhibited L-type calcium current (I) and peak sodium current (I) with IC values of 137.06 and 559.80 μmol/L, respectively. Application of barbaloin (100, 200 μmol/L) decreased ATX II-enhanced late sodium current (I) by 36.6%±3.3% and 71.8%±6.5%, respectively. However, barbaloin up to 800 μmol/L did not affect the inward rectifier potassium current (I) or the rapidly activated delayed rectifier potassium current (I) in ventricular myocytes. In Langendorff-perfused rabbit hearts, barbaloin (200 μmol/L) significantly inhibited aconitine-induced ventricular arrhythmias. These results demonstrate that barbaloin has potential as an antiarrhythmic drug.

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Section: Discussionmentioning

confidence: 99%

Barbaloin inhibits ventricular arrhythmias in rabbits by modulating voltage-gated ion channels

et al. 2017

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“…The accumulation of Ca 2+ can cause cell injury, electrical activity disorder and ventricular systolic dysfunction, which aggravates myocardial ischemia and hypoxia. The entire process can develop into a vicious circle [3,4,13,14] . Our previous study indicates that 2 µmol/L TTX (no report regarding its effects on ion channels except I Na.L ) suppresses the reverse I NCX under normal and hypoxic conditions by inhibiting I Na.L [11] .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies indicated that late sodium current (I Na.L ), which is tetrodotoxin (TTX)-sensitive [1] , was increased under various pathological conditions, such as long QT syndrome III, myocardial hypertrophy, heart failure, ischemia, anoxia, and oxidative stress [2][3][4][5][6][7][8][9][10] . Although it has a much smaller amplitude than the transient sodium current (I Na.T ) under normal conditions, I Na.L plays an important role in determining the plateau of action potential (AP) and action potential duration (APD) under the above pathological conditions [11,12] .…”

Section: Introductionmentioning

confidence: 99%

Tolterodine reduces veratridine-augmented late INa, reverse-INCX and early afterdepolarizations in isolated rabbit ventricular myocytes

Wang

Zhang

et al. 2016

Acta Pharmacol Sin

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Aim: The augmentation of late sodium current (I Na.L ) not only causes intracellular Na + accumulation, which results in intracellular Ca 2+ overload via the reverse mode of the Na + /Ca 2+ exchange current (reverse-I NCX ), but also prolongs APD and induces early afterdepolarizations (EAD), which can lead to arrhythmia and cardiac dysfunction. Thus, the inhibition of I Na.L is considered to be a potential way for therapeutic intervention in ischemia and heart failure. In this study we investigated the effects of tolterodine (Tol), a competitive muscarinic receptor antagonist, on normal and veratridine (Ver)-augmented I Na.L , reverse-I NCX and APD in isolated rabbit ventricular myocytes, which might contribute to its cardioprotective activity. Methods: Rabbit ventricular myocytes were prepared. The I Na.L and reverse-I NCX were recorded in voltage clamp mode, whereas action potentials and Ver-induced early afterdepolarizations (EADs) were recorded in current clamp mode. Drugs were applied via superfusion. Results: Tol (3-120 nmol/L) concentration-dependently inhibited the normal and Ver-augmented I Na.L with IC 50 values of 32.08 nmol/L and 42.47 nmol/L, respectively. Atropine (100 μmol/L) did not affect the inhibitory effects of Tol (30 nmol/L) on Ver-augmented I Na.L . In contrast, much high concentrations of Tol was needed to inhibit the transient sodium current (I Na.T ) with an IC 50 value of 183.03 μmol/L. In addition, Tol (30 nmol/L) significantly shifted the inactivation curve of I Na.T toward a more depolarizing membrane potential without affecting its activation characteristics. Moreover, Tol (30 nmol/L) significantly decreased Ver-augmented reverse-I NCX . Tol (30 nmol/L) increased the action potential duration (APD) by 16% under the basal conditions. Ver (20 μmol/L) considerably extended the APD and evoked EADs in 18/24 cells (75%). In the presence of Ver, Tol (30 nmol/L) markedly decreased the APD and eliminated EADs (0/24 cells). Conclusion: Tol inhibits normal and Ver-augmented I NaL and decreases Ver-augmented reverse-I NCX . In addition, Tol reverses the prolongation of the APD and eliminates the EADs induced by Ver, thus prevents Ver-induced arrhythmia.

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“…Effects of SH on I Na.L I Na.L was enhanced under many pathological conditions and ATX II, an I Na.L opener, was commonly used as the model drug in I Na.L -enhanced experiments [10,[12][13][14][15]. Therefore, the effects of SH on I Na.L were examined in ventricular myocytes under control and ATX II-treated conditions.…”

Section: Effects Of Sh On Steady State Activation and Inactivation Ofmentioning

confidence: 97%

“…It has been reported that I Na.L was increased under many pathological conditions, including myocardial hypertrophy, ventricular remodeling, heart failure, hypoxia, and ischemia [8][9][10][11]. In addition, our previous study demonstrated that increases in I Na.L elevated (Na + ) i and consequently contributed to the development of intracellular Ca 2+ overload by enhancing I NCX [8,15] Effects of SH on steady state activation and inactivation of I Na.P in rabbit ventricular myocytes. a Representative traces of I Na.P steady state inactivation in the control and 100 μmol/L SH-treated groups.…”

Section: Effects Of Sh On the Amplitude Of I Krmentioning

confidence: 99%

Sodium Houttuyfonate Inhibits Voltage-Gated Peak Sodium Current and Anemonia Sulcata Toxin II-Increased Late Sodium Current in Rabbit Ventricular Myocytes

et al. 2018

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Aim: Sodium houttuyfonate (SH), a chemical compound originating from Houttuynia cordata, has been reported to have anti-inflammatory, antibacterial, and antifungal effects, as well as cardioprotective effects. In this study, we investigated the effects of SH on cardiac electrophysiology, because to the best of our knowledge, this issue has not been previously investigated. Methods: We used the whole-cell patch-clamp technique to explore the effects of SH on peak sodium current (I_Na.P) and late sodium current (I_Na.L) in isolated rabbit ventricular myocytes. To test the drug safety of SH, we also investigated the effect of SH on rapidly activated delayed rectifier potassium current (I_Kr). Results: SH (1, 10, 50, and 100 μmol/L) inhibited I_Na.P in a concentration-dependent manner with an IC₅₀ of 78.89 μmol/L. In addition, SH (100 μmol/L) accelerated the steady state inactivation of I_Na.P. Moreover, 50 and 100 μmol/L SH inhibited Anemonia sulcata toxin II (ATX II)-increased I_Na.L by 30.1 and 57.1%, respectively. However, SH (50 and 100 μmol/L) only slightly affected I_Kr. Conclusions: The inhibitory effects of SH on ATX II-increased I_Na.L may underlie the electrophysiological mechanisms of the cardioprotective effects of SH; SH has the potential to be an effective and safe antiarrhythmic drug.

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Ketamine attenuates the Na+-dependent Ca2+ overload in rabbit ventricular myocytes in vitro by inhibiting late Na+ and L-type Ca2+ currents

Cited by 12 publications

References 49 publications

Barbaloin inhibits ventricular arrhythmias in rabbits by modulating voltage-gated ion channels

Barbaloin inhibits ventricular arrhythmias in rabbits by modulating voltage-gated ion channels

Tolterodine reduces veratridine-augmented late INa, reverse-INCX and early afterdepolarizations in isolated rabbit ventricular myocytes

Sodium Houttuyfonate Inhibits Voltage-Gated Peak Sodium Current and Anemonia Sulcata Toxin II-Increased Late Sodium Current in Rabbit Ventricular Myocytes

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