Block of hERG K+ channel and prolongation of action potential duration by fluphenazine at submicromolar concentration

2013 ◽  
Vol 702 (1-3) ◽  
pp. 165-173 ◽  
Author(s):  
Hee-Kyung Hong ◽  
Byung Hoon Lee ◽  
Mi-Hyeong Park ◽  
Seung Ho Lee ◽  
Daehyun Chu ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
K Channel ◽  
Prolongation Of Action Potential

scholarly journals Synapse-Level Determination of Action Potential Duration by K + Channel Clustering in Axons

Neuron ◽  
2016 ◽  
Vol 91 (2) ◽  
pp. 370-383 ◽  
Author(s):  
Matthew J.M. Rowan ◽  
Gina DelCanto ◽  
Jianqing J. Yu ◽  
Naomi Kamasawa ◽  
Jason M. Christie
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
K Channel

Sprint training shortens prolonged action potential duration in postinfarction rat myocyte: mechanisms

2001 ◽  
Vol 90 (5) ◽  
pp. 1720-1728 ◽  
Author(s):  
Xue-Qian Zhang ◽  
Lian-Qin Zhang ◽  
Bradley M. Palmer ◽  
Yuk-Chow Ng ◽  
Timothy I. Musch ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Outward Current ◽  
Activation Parameters ◽  
Resting Membrane Potential ◽  
Transient Outward Current ◽  
Sprint Training ◽  
Myocyte Hypertrophy ◽  
Dependent Inactivation ◽  
Prolongation Of Action Potential

Two electrophysiological manifestations of myocardial infarction (MI)-induced myocyte hypertrophy are prolongation of action potential duration (APD) and reduction of transient outward current ( I to) density. Because high-intensity sprint training (HIST) ameliorated myocyte hypertrophy and improved myocyte Ca2+ homeostasis and contractility after MI, the present study evaluated whether 6–8 wk of HIST would shorten the prolonged APD and improve the depressed I to in post-MI myocytes. There were no differences in resting membrane potential and action potential amplitude (APA) measured in myocytes isolated from sham-sedentary (Sed), MI-Sed, and MI-HIST groups. Times required for repolarization to 50 and 90% APA were significantly ( P < 0.001) prolonged in MI-Sed myocytes. HIST reduced times required for repolarization to 50 and 90% APA to values observed in Sham-Sed myocytes. The fast and slow components of I towere significantly ( P < 0.0001) reduced in MI-Sed myocytes. HIST significantly ( P < 0.001) enhanced the fast and slow components of I to in MI myocytes, although not to levels observed in Sham-Sed myocytes. There were no significant differences in steady-state I toinactivation and activation parameters among Sham-Sed, MI-Sed, and MI-HIST myocytes. Likewise, recovery from time-dependent inactivation was also similar among the three groups. We suggest that normalization of APD after MI by HIST may be mediated by restoration of I to toward normal levels.

Class III Antiarrhythmic Effects of Dofetilide in Rabbit Atrial Myocardium

1996 ◽  
Vol 1 (3) ◽  
pp. 229-234 ◽  
Author(s):  
Regan T. Pallandi ◽  
Nigel H. Lovell ◽  
Terence J. Campbell
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Interstimulus Interval ◽  
Class Iii ◽  
Atrial Myocardium ◽  
New Class ◽  
Class Iii Antiarrhythmic Agent ◽  
Prolongation Of Action Potential ◽  
Dose Dependent ◽  
Microelectrode Techniques

Background Dofetilide is a new class III antiarrhythmic agent with demonstrated efficacy in ventricular and atrial tachyarrhythmias. We investigated its class HI actions and their modulation by stimulation rate in rabbit atrial myocardium. Methods and Results Standard microelectrode techniques were used to record action potentials from rabbit atrial tissue at varying stimulation rates. Dofetilide produced a dose-dependent prolongation of action potential duration at concentrations from 1 nM to 1 μM at an interstimulus interval of 1000 ms. Action potential duration at 90% repolarization (action potential duration) was prolonged from 116 ± 11.7 ms in control solutions to 148 ± 13.9 ms at 1nM dofetilide and 186 ± 49.3 ms at 1 μM dofetilide ( P < .05 for 1 nM vs control; P < .01 for 1 μM vs control). Reduction of interstimulus interval to 500 ms had no significant effect on action potential duration prolongation by dofetilide. At faster rates than this, and particularly at an interstimulus interval less than 330 ms, a marked “reverse rate dependence” of the class III effect was observed. Specifically, the high therapeutic concentration of 10 nM showed no effect on action potential duration at interstimulus interval of 250 ms or 200 ms, and even at a concentration of 30 nM, the small class III effect was no longer statistically significant at these rates. Conclusion Dofetilide prolongs action potential duration in rabbit atrial myocardium, but this effect is significantly attenuated at stimulation rates above 2 Hz.

Exaggerated block of hERG (KCNH2) and prolongation of action potential duration by erythromycin at temperatures between 37°C and 42°C

Heart Rhythm ◽  
2005 ◽  
Vol 2 (8) ◽  
pp. 860-866 ◽  
Author(s):  
Jiqing Guo ◽  
Shu Zhan ◽  
James P. Lees-Miller ◽  
GuoQi Teng ◽  
Henry J. Duff
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Prolongation Of Action Potential

scholarly journals Inhibition of Histone Deacetylases Induces K+ Channel Remodeling and Action Potential Prolongation in HL-1 Atrial Cardiomyocytes

2018 ◽  
Vol 49 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Patrick Lugenbiel ◽  
Katharina Govorov ◽  
Ann-Kathrin Rahm ◽  
Teresa Wieder ◽  
Dominik Gramlich ◽  
...  
Keyword(s):  
Action Potential ◽  
Ion Channel ◽  
Action Potential Duration ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Class I ◽  
K Channel ◽  
Hdac Inhibition ◽  
Atrial Cardiomyocytes ◽  
Channel Expression

Background/Aims: Cardiac arrhythmias are triggered by environmental stimuli that may modulate expression of cardiac ion channels. Underlying epigenetic regulation of cardiac electrophysiology remains incompletely understood. Histone deacetylases (HDACs) control gene expression and cardiac integrity. We hypothesized that class I/II HDACs transcriptionally regulate ion channel expression and determine action potential duration (APD) in cardiac myocytes. Methods: Global class I/II HDAC inhibition was achieved by administration of trichostatin A (TSA). HDAC-mediated effects on K+ channel expression and electrophysiological function were evaluated in murine atrial cardiomyocytes (HL-1 cells) using real-time PCR, Western blot, and patch clamp analyses. Electrical tachypacing was employed to recapitulate arrhythmia-related effects on ion channel remodeling in the absence and presence of HDAC inhibition. Results: Global HDAC inhibition increased histone acetylation and prolonged APD90 in atrial cardiomyocytes compared to untreated control cells. Transcript levels of voltage-gated or inwardly rectifying K+ channels Kcnq1, Kcnj3 and Kcnj5 were significantly reduced, whereas Kcnk2, Kcnj2 and Kcnd3 mRNAs were upregulated. Ion channel remodeling was similarly observed at protein level. Short-term tachypacing did not induce significant transcriptional K+ channel remodeling. Conclusion: The present findings link class I/II HDAC activity to regulation of ion channel expression and action potential duration in atrial cardiomyocytes. Clinical implications for HDAC-based antiarrhythmic therapy and cardiac safety of HDAC inhibitors require further investigation.

Electrophysiologic Effect of Desflurane on the Prolongation of Action Potential Duration in Ventricular Myocytes

2006 ◽  
Vol 50 (5) ◽  
pp. 557
Author(s):  
Sun Jun Bae ◽  
Myung Hee Kim ◽  
Jee Eun Chae ◽  
Chong Hoon Kim ◽  
Kyung Tae Min ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Ventricular Myocytes ◽  
Prolongation Of Action Potential

scholarly journals Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells

2011 ◽  
Vol 106 (1) ◽  
pp. 144-152 ◽  
Author(s):  
Yu Liu ◽  
Iaroslav Savtchouk ◽  
Shoana Acharjee ◽  
Siqiong June Liu
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Channel Blocker ◽  
Stellate Cells ◽  
Bk Channels ◽  
Bk Channel ◽  
K Channel ◽  
Duration Of Action

Many fast-spiking inhibitory interneurons, including cerebellar stellate cells, fire brief action potentials and express α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors (AMPAR) that are permeable to Ca2+ and do not contain the GluR2 subunit. In a recent study, we found that increasing action potential duration promotes GluR2 gene transcription in stellate cells. We have now tested the prediction that activation of potassium channels that control the duration of action potentials can suppress the expression of GluR2-containing AMPARs at stellate cell synapses. We find that large-conductance Ca2+-activated potassium (BK) channels mediate a large proportion of the depolarization-evoked noninactivating potassium current in stellate cells. Pharmacological blockade of BK channels prolonged the action potential duration in postsynaptic stellate cells and altered synaptic AMPAR subtype from GluR2-lacking to GluR2-containing Ca2+-impermeable AMPARs. An L-type channel blocker abolished an increase in Ca2+ entry that was associated with spike broadening and also prevented the BK channel blocker-induced switch in AMPAR phenotype. Thus blocking BK potassium channels prolongs the action potential duration and increases the expression of GluR2-containing receptors at the synapse by enhancing Ca2+ entry in cerebellar stellate cells.

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