State-dependent dissociation of HERG channel inhibitors
نویسندگان
چکیده
منابع مشابه
State dependent dissociation of HERG channel inhibitors.
BACKGROUND AND PURPOSE Inhibition of HERG channels prolongs the ventricular action potential and the QT interval with the risk of torsade de pointes arrhythmias and sudden cardiac death. Many drugs induce greater inhibition of HERG channels when the cell membrane is depolarized frequently. The dependence of inhibition on the pulsing rate may yield different IC(50) values at different frequencie...
متن کاملState Dependent Multi channel Queuing System with Ordered Entry
In the present study, we analyze the multi-channel service system with ordered entryfrom finite-source and finite-storage at each channel. The arrival and service rates are assumedto be state dependent. The steady state probabilities of the system are obtained by usingChapmann-Kolmogorov equations. Some other performance indices viz. utilization of servers,expected number of units in the system...
متن کاملNew potential binding determinant for hERG channel inhibitors
Human ether-à-go-go related gene (hERG) 1 channels conduct the rapid delayed rectifier K(+) current (IKr) and are essential for the repolarization of the cardiac action potential. hERG1 inhibition by structurally diverse drugs may lead to life threatening arrhythmia. Putative binding determinants of hERG1 channel blockers include T623, S624 and V625 on the pore helix, and residues G648, Y652 an...
متن کاملUse-dependent 'agonist' effect of azimilide on the HERG channel.
Azimilide (AZ) is a class III antiarrhythmic drug that has voltage-dependent dual effects on the HERG channel: 1) increasing current amplitude at low-voltage depolarization (agonist effect), and 2) suppressing current at more depolarized voltages (antagonist effect). We examined the mechanism for the agonist effect of AZ on HERG expressed in Xenopus oocytes. The agonist effect resulted from an ...
متن کاملDissociative States: hERG Channel (Kv11.1) Modulators That Enhance Dissociation of Drugs From Their Blocking Receptor
Sudden cardiac death secondary to drug-induced long QT syndrome is a major safety concern and has led to withdrawal of several high-profile drugs, such as cisapride and astemizole, from the market. Although these drugs have different chemical structures, they all block the rapid delayed rectifier K current (I Kr ) with high potency. The hERG channel (Kv11.1) encoded by the hERG gene is responsi...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: BMC Pharmacology
سال: 2007
ISSN: 1471-2210
DOI: 10.1186/1471-2210-7-s2-a13