JZTX-V Targets the Voltage Sensor in Kv4.2 to Inhibit Ito Potassium Channels in Cardiomyocytes

JZTX-V Targets the Voltage Sensor in Kv4.2 to Inhibit Ito Potassium Channels in Cardiomyocytes Yiya Zhang1,2,3*, Ji Luo3, Juan He3, Mingqiang Rong3 and Xiongzhi Zeng3* 1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China 2Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China 3The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China Kv4 potassium channels are responsible for transient outward K+ currents in the cardiac action potential (AP). Previous experiments by our group demonstrated that Jingzhaotoxin-V (JZTX-V) selectively inhibits A-type potassium channels. However, the specific effects of JZTX-V on the transient outward (Ito) current of cardiomyocytes and underlying mechanism of action remain unclear. In the current study, 100 nM JZTX-V effectively inhibited the Ito current and extended the action potential duration (APD) of neonatal rat ventricular myocytes (NRVM). We further analyzed the effects of JZTX-V on Kv4.2, a cloned channel believed to underlie the Ito current in rat cardiomyocytes. JZTX-V inhibited the Kv4.2 current with a half-maximal inhibitory concentration (IC50) of 13 ± 1.7 nM. To establish the molecular mechanism underlying the inhibitory action of JZTX-V on Kv4.2, we performed alanine scanning mutagenesis of Kv4.2 and JZTX-V and asse...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
We describe a contiguous gene deletion of the ATM locus in a multi-generation family of Italian descent with a strong family history of pancreatic cancer. A deletion of one copy of the entire ATM gene was identified by routine panel testing and further characterized by chromosomal microarray analysis. An 11q22.3 microdeletion of approximately 960kb was identified that is predicted to result in loss of 10 genes including ATM. The deletion was identified in two additional family members including a presymptomatic daughter and an affected sibling. A normal disomic complement of the 11q22.3 region was detected in a third famil...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research
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Source: Anaesthesia, Critical Care and Pain Medicine - Category: Anesthesiology Source Type: research
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Source: Anaesthesia, Critical Care and Pain Medicine - Category: Anesthesiology Source Type: research
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Source: Brazilian Journal of Anesthesiology - Category: Anesthesiology Source Type: research
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Source: The Journal of Allergy and Clinical Immunology: In Practice - Category: Allergy & Immunology Source Type: research
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Source: The Journal of Allergy and Clinical Immunology: In Practice - Category: Allergy & Immunology Source Type: research
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Source: Revista Espanola de Medicina Nuclear e Imagen Molecular - Category: Nuclear Medicine Source Type: research
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Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
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Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
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