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• W2938542016 startingPage "106575" @default.
• W2938542016 abstract "High throughput in vitro profiling of the cardiac Nav1.5 peak sodium current (INa) is widely used in cardiac safety screening. However, there is no standardized high throughput method to measure late INa. This study assessed the pharmacological and biophysical properties of veratridine and ATX-II, as well as the channel mutation (Nav1.5-∆KPQ) on the late INa. We describe a method for simultaneous measurement of both peak and late INa. The planar patch clamp technique (QPatch) was applied to record the peak and late INa. The Nav1.5-∆KPQ mutant produced a small late INa (41.9 ± 5.4 pA) not large enough to enable compound profiling. In contrast in wild type Nav1.5 expressing cells veratridine (100 μM) and ATX-II (100 nM) enhanced concentration-dependent increases in the late INa (maximum responses of 1162.2 ± 258.5 pA and 392.4 ± 71.3 pA, respectively). Veratridine inhibited, whereas, ATX-II had a minimal effect, on the peak INa and preserved the current-voltage curve. Peak and late INa inhibition was characterized for 25 clinical INa blockers in the presence of ATX-II. Compound IC50 values for peak INa generated in the absence or presence of ATX-II correlated. The potency of the late INa block was found to be dependent on whether it was measured at the end of the depolarizing pulse or during the ramp. In the presence of ATX-II, both peak and late INa could be assessed simultaneously. Late INa may be best assessed using the maximum response obtained during the ramp of the voltage protocol." @default.
• W2938542016 created "2019-04-25" @default.
• W2938542016 creator A5006173892 @default.
• W2938542016 creator A5031121778 @default.
• W2938542016 date "2019-09-01" @default.
• W2938542016 modified "2023-10-18" @default.
• W2938542016 title "Simultaneous assessment of compound activity on cardiac Nav1.5 peak and late currents in an automated patch clamp platform" @default.
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• W2938542016 doi "https://doi.org/10.1016/j.vascn.2019.04.001" @default.
• W2938542016 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30999054" @default.
• W2938542016 hasPublicationYear "2019" @default.
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