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Protriptyline inhibits KCNH2. 14 / 15
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"Therefore, to understand the mechanisms underlying protriptyline induced electrophysiological changes in the action potential and ECG, it is important to determine the effects of this drug on ion chan[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The HERG-current inhibition by 50 muM protriptyline at different voltages (- 40, - 20, 0, + 20, and + 40 mV) was 10.2% +/- 10.1%, 20.6% +/- 6.1%, 27.7% +/- 2.4%, 35.1% +/- 2.7%, and 50.2% +/- 6.7%, re[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Taken together, protriptyline inhibits HERG channels predominantly in the open and inactivated state rather than in the closed state.To examine the use-dependence of the protriptyline effect, HERG cha[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"To address the question of whether HERG channels are also blocked by protriptyline in its inactivated state, a long test pulse to + 80 mV (4 s) from a holding potential of - 90 mV was applied to inact[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In this study, we used the HERG channel expressed in Xenopus oocytes or HEK cells to test whether protriptyline would block the HERG channel and to examine inhibiting mechanisms.HERG (accession no."
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"We found that the time course of the channel blockade was dependent on the activation frequency, with HERG blockade by protriptyline occurring more quickly at higher activation frequencies."
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"In this series of experiments, 50 muM protriptyline reduced HERG outward currents at the end of the 0 mV pulse by 45.1% +/- 5.0% (n = 8)."
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"HERG blockade by protriptyline was use dependent, exhibiting a more rapid onset and a greater steady-state block at higher frequencies of activation."
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"Additionally, at the beginning of the pulse, the fractional sustained current (obtained by normalizing the currents with protriptyline relative to control currents) was 0.87 +/- 0.05 of the control (n[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"We found that protriptyline blocked HERG in a mammalian cell line with an IC 50 of ~ 1.1 muM, which is at the supra-therapeutic level compared with the reports of both the therapeutic serum concentrat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Taken together, these results indicate that it is necessary to test each TCA experimentally to evaluate its potential to block the HERG channel since the HERG blocking potencies and inhibitory mechani[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Computer simulation of HERG blocking by protriptyline suggested that protriptyline binds the HERG channel at the internal chamber and makes a hydrogen bond to the carbonyl oxygen of Leu622."
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"The IC (50) for protriptyline block of HERG current in Xenopus oocytes progressively decreased relative to the degree of depolarization, from 142.0 microM at -40 mV to 91.7 microM at 0 mV to 52.9 microM at +40 mV."
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"This raises the possibility that protriptyline may prolong the action potential duration in vivo, and may increase the QT interval by inhibiting the HERG current, which can eventually result in torsad[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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