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A-935142 activates KCNH2. 14 / 14
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"We investigated the possibility that A-935142 could enhance hERG current in the presence of sotalol."
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"This study showed A-935142 enhanced hERG current in the presence of sotalol (57.5 ± 5.8%) to a similar extent as that seen with A-935142 alone (55.6%, see Fig. 2 ; p = 0.511 vs. Fig. 4 A, unpaired t -[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"A-935142 increased tail current amplitudes at test voltages positive to the reversal potential, reducing the rectification of hERG current."
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"The present study provides pharmacological evidence suggesting that A-935142 enhances hERG current by interacting with the channel at a site different from typical hERG channel blockers."
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"This effect on the slope conductance suggests that A-935142 may increase the single-channel conductance of hERG channel.We also analyzed the time course of recovery from inactivation by applying a mon[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Sotalol blocked A-935142 enhanced hERG current 43.5 ± 1.5% (measurement made relative to peak of enhanced current), similar to the amount of hERG current block elicited by sotalol alone (p = 0.193 sot[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Specifically, A-935142 induced three distinct changes in hERG channel gating: (a) facilitating activation (a negative shift of the voltage-dependence of activation and accelerated activation kinetics)[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"A member of the series, A-935142 ({4-[4-(5-trifluoromethyl-1H-pyrazol-3-yl)-phenyl]-cyclohexyl}-acetic acid), enhanced hERG current 55.6 ±5.1% at 60 μM."
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"Practically, the present study shows that functional hERG current assays are necessary to detect hERG current enhancers such as A-935142."
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"Similar to previously reported activators, A-935142 significantly increased outward hERG current (including step and tail current) ( Figs."
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"Further analysis revealed that hERG current enhancement by A-935142 is steeply voltage-dependent in the range of −50 to −20 mV (inset in Fig. 2 D), consistent with a leftward shift in the voltage-depe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"10 A-935142 slows hERG channel deactivation at multiple voltage potentials."
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"Finally, it is also interesting to note that none of the reported hERG activators (including A-935142) demonstrate any significant effects on the rate of recovery from inactivation of hERG channel."
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"In summary, A-935142 increases hERG current by complex mechanisms."
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