Browsing by Author "Wang, Zhuo"

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Effects of ondansetron on apamin-sensitive small conductance calcium-activated potassium currents in pacing-induced failing rabbit hearts
(2020-02-01)
Yin, Dechun
;
Yang, Na
;
Tian, Zhipeng
;
Wu, Adonis Z.
;
Xu, Dongzhu
BACKGROUND Ondansetron, a widely prescribed antiemetic, has been implicated in drug-induced long QT syndrome. Recent patch clamp experiments have shown that ondansetron inhibits the apamin-sensitive small conductance calcium-activated potassium current (I-KAS). OBJECTIVE The purpose of this study was to determine whether ondansetron causes action potential duration (APD) prolongation by I-KAS inhibition. METHODS Optical mapping was performed in rabbit hearts with pacing-induced heart failure (HF) and in normal hearts before and after ondansetron (100 nM) infusion. APD at 80% repolarization (APD(80)) and arrhythmia inducibility were determined. Additional studies with ondansetron were performed in normal hearts perfused with hypokalemic Tyrode's (2.4 mM) solution before or after apamin administration. RESULTS The corrected QT interval in HF was 326 ms (95% confidence interval [CI] 306-347 ms) at baseline and 364 ms (95% CI 351-378 ms) after ondansetron infusion (P < .001). Ondansetron significantly prolonged APD(80) in the HF group and promoted early afterdepolarizations, steepened the APD restitution curve, and increased ventricular vulnerability. Ventricular fibrillation was not inducible in HF ventricles at baseline, but after ondansetron infusion, ventricular fibrillation was induced in 5 of the 7 ventricles (P = .021). In hypokalemia, apamin prolonged APD(80) from 163 ms (95% CI 146-180 ms) to 180 ms (95% CI 156-204 ms) (P = .018). Subsequent administration of ondansetron failed to further prolong APD(80) (180 ms [95% CI 156-204 ms] vs 179 ms [95% CI 165-194 ms]; P = .789). The results were similar when ondansetron was administered first, followed by apamin. CONCLUSION Ondansetron is a specific I-KAS blocker at therapeutic concentrations. Ondansetron may prolong the QT interval in HF by inhibiting small conductance calcium-activated potassium channels, which increases the vulnerability to ventricular arrhythmias.
Giant photoluminescence enhancement in tungsten-diselenide-gold plasmonic hybrid structures
(2016-05-01)
Wang, Zhuo
;
Dong, Zhaogang
;
Gu, Yinghong
;
Chang, Yung-Huang
;
Zhang, Lei
Impressive properties arise from the atomically thin nature of transition metal dichalcogenide two-dimensional materials. However, being atomically thin limits their optical absorption or emission. Hence, enhancing their photoluminescence by plasmonic nanostructures is critical for integrating these materials in optoelectronic and photonic devices. Typical photoluminescence enhancement from transition metal dichalcogenides is 100-fold, with recent enhancement of 1,000-fold achieved by simultaneously enhancing absorption, emission and directionality of the system. By suspending WSe2 flakes onto sub-20-nm-wide trenches in gold substrate, we report a giant photoluminescence enhancement of similar to 20,000-fold. It is attributed to an enhanced absorption of the pump laser due to the lateral gap plasmons confined in the trenches and the enhanced Purcell factor by the plasmonic nanostructure. This work demonstrates the feasibility of giant photoluminescence enhancement in WSe2 with judiciously designed plasmonic nanostructures and paves a way towards the implementation of plasmon-enhanced transition metal dichalcogenide photodetectors, sensors and emitters.
Sex-specific activation of SK current by isoproterenol facilitates action potential triangulation and arrhythmogenesis in rabbit ventricles
(2018-09-15)
Chen, Mu
;
Yin, Dechun
;
Guo, Shuai
;
Xu, Dong-Zhu
;
Wang, Zhuo
Sex has a large influence on cardiac electrophysiological properties. Whether sex differences exist in apamin-sensitive small conductance Ca2+-activated K+ (SK) current (I-KAS) remains unknown. We performed optical mapping, transmembrane potential, patch clamp, western blot and immunostaining in 62 normal rabbit ventricles, including 32 females and 30 males. I-KAS blockade by apamin only minimally prolonged action potential (AP) duration (APD) in the basal condition for both sexes, but significantly prolonged APD in the presence of isoproterenol in females. Apamin prolonged APD at the level of 25% repolarization (APD(25)) more prominently than APD at the level of 80% repolarization (APD(80)), consequently reversing isoproterenol-induced AP triangulation in females. In comparison, apamin prolonged APD to a significantly lesser extent in males and failed to restore the AP plateau during isoproterenol infusion. I-KAS in males did not respond to the L-type calcium current agonist BayK8644, but was amplified by the casein kinase 2 (CK2) inhibitor 4,5,6,7-tetrabromobenzotriazole. In addition, whole-cell outward I-KAS densities in ventricular cardiomyocytes were significantly larger in females than in males. SK channel subtype 2 (SK2) protein expression was higher and the CK2/SK2 ratio was lower in females than in males. I-KAS activation in females induced negative intracellular Ca2+-voltage coupling, promoted electromechanically discordant phase 2 repolarization alternans and facilitated ventricular fibrillation (VF). Apamin eliminated the negative Ca2+-voltage coupling, attenuated alternans and reduced VF inducibility, phase singularities and dominant frequencies in females, but not in males. We conclude that beta-adrenergic stimulation activates ventricular I-KAS in females to a much greater extent than in males. I-KAS activation plays an important role in ventricular arrhythmogenesis in females during sympathetic stimulation.