Novel, Potent Inhibitors of Human Kv1.5 K+ Channels and Ultrarapidly Activating Delayed Rectifier Potassium Current

2006 ◽  
Vol 317 (3) ◽  
pp. 1054-1063 ◽  
Author(s):  
Armando Lagrutta ◽  
Jixin Wang ◽  
Bernard Fermini ◽  
Joseph J. Salata
Keyword(s):  
Potassium Current ◽  
Delayed Rectifier ◽  
K Channels ◽  
Delayed Rectifier Potassium Current

scholarly journals Excavatolide-B Enhances Contextual Memory Retrieval via Repressing the Delayed Rectifier Potassium Current in the Hippocampus

Marine Drugs ◽  
2018 ◽  
Vol 16 (11) ◽  
pp. 405 ◽  
Author(s):  
Irene Huang ◽  
Yu-Luan Hsu ◽  
Chien-Chang Chen ◽  
Mei-Fang Chen ◽  
Zhi-Hong Wen ◽  
...  
Keyword(s):  
Memory Retrieval ◽  
Potassium Current ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Autism Spectrum ◽  
Absence Epilepsy ◽  
Delayed Rectifier ◽  
Contextual Memory ◽  
Term Potentiation ◽  
Delayed Rectifier Potassium Current

Memory retrieval dysfunction is a symptom of schizophrenia, autism spectrum disorder (ASD), and absence epilepsy (AE), as well as an early sign of Alzheimer’s disease. To date, few drugs have been reported to enhance memory retrieval. Here, we found that a coral-derived natural product, excavatolide-B (Exc-B), enhances contextual memory retrieval in both wild-type and Cav3.2−/− mice via repressing the delayed rectifier potassium current, thus lowering the threshold for action potential initiation and enhancing induction of long-term potentiation (LTP). The human CACNA1H gene encodes a T-type calcium channel (Cav3.2), and its mutation is associated with schizophrenia, ASD, and AE, which are all characterized by abnormal memory function. Our previous publication demonstrated that Cav3.2−/− mice exhibit impaired contextual-associated memory retrieval, whilst their retrieval of spatial memory and auditory cued memory remain intact. The effect of Exc-B on enhancing the retrieval of context-associated memory provides a hope for novel drug development.

scholarly journals Slow Delayed Rectifier Potassium Current Blockade Contributes Importantly to Drug-Induced Long QT Syndrome

2013 ◽  
Vol 6 (5) ◽  
pp. 1002-1009 ◽  
Author(s):  
Christiaan C. Veerman ◽  
Arie O. Verkerk ◽  
Marieke T. Blom ◽  
Christine A. Klemens ◽  
Pim N.J. Langendijk ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Potassium Current ◽  
Delayed Rectifier ◽  
Long Qt ◽  
Drug Induced ◽  
Delayed Rectifier Potassium Current ◽  
Qt Syndrome

scholarly journals P938Regulation of the delayed rectifier potassium current during the adrenergic adaptation of cardiomyocytes

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
D Kiss ◽  
T Hezso ◽  
B Kurtan ◽  
R Veress ◽  
D Baranyai ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Potassium Current ◽  
Slow Component ◽  
Delayed Rectifier ◽  
Total Charge ◽  
Current Profile ◽  
Calcium Calmodulin Dependent ◽  
Delayed Rectifier Potassium Current ◽  
Innovation And Technology ◽  
Dependent Protein

Abstract Funding Acknowledgements Supported by the ÚNKP-19-3 New National Excellence program of the Ministry for Innovation and Technology Introduction and aims Adaptation of the human heart to physical activity is a complex mechanism that includes the change of heart rate, morphology of the action potential (AP) among others. Stimulation of β-adrenergic receptors (β-AR) causes the shortening of the AP duration of ventricular cardiomyocytes. This is caused by the regulation of the potassium currents by the β-adrenergic signaling pathway. Our aim was to investigate the role of protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII) in the regulation of the slow component (IKs) of the delayed rectifier potassium current under β-AR activation. Methods Our experiments were performed on isolated canine cardiomyocytes from the left ventricle. The IKs current profile was determined under a ventricular AP. We used "AP voltage clamp" conditions in six experimental groups: Control (CTRL), β-AR stimulation with isoproterenol (ISO), CaMKII inhibition with KN-93 (KN-93), PKA inhibition with H-89 (H-89) β-AR stimulation with inhibited CaMKII (KN-93 + ISO), β-AR stimulation with inhibited PKA (H-89 + ISO). β-AR stimulation with inhibited CaMKII and PKA (KN-93 + H-89 + ISO) Results The highest current density of IKs was approximately 6 times higher and the charge delivered by IKs was about 8 times larger in the ISO group than in CTRL or KN-93 conditions. In the KN-93 + ISO group, IKs amplitude was about 60% smaller and delivered about half the total charge compared to the ISO group. In the H‑89 + ISO group, IKs was about 30% smaller and delivered 40% less total charge than in the ISO group. In the KN-93 + H-89 + ISO group the IKs did not changed sicnificantly. Conclusion Based on our results, CaMKII plays an important role in regulating IKs by β-AR stimulation.

Olanzapine prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current

2006 ◽  
Vol 21 (7) ◽  
pp. 735-741 ◽  
Author(s):  
Pierre Morissette ◽  
Raymond Hreiche ◽  
Louise Mallet ◽  
Dean Vo ◽  
Edward E. Knaus ◽  
...  
Keyword(s):  
Potassium Current ◽  
Delayed Rectifier ◽  
Cardiac Repolarization ◽  
Delayed Rectifier Potassium Current
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