Evidence for state-dependent block of DPI 201-106, a synthetic inhibitor of NA+ channel inactivation, on delayed-rectifier K+ current in pituitary tumor (GH3) cells

Y. J. Wang, M. W. Lin, A. A. Lin, H. Peng, Sheng Nan Wu

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16 Citations (Scopus)

Abstract

DPI 201-107 (DPI), a diphenylpiperazinylindole derivative, was reported to be a cardio-selective modifier of voltage-gated Na+ channels. It remains unclear whether DPI has any effects on ion currents. The effects of DPI on ion currents and membrane potential in pituitary tumor (GH3) cells were investigated in this study. DPI (1-100 μM) suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in a concentration-dependent manner with an IC50 value of 9.4 μM. The presence of DPI also enhanced the rate and extent of IK(DR) inactivation. Recovery from block by DPI (10 μM) was fitted by a single exponential. Crossover of tail currents during the exposure to DPI was also observed. Under current-clamp recordings, DPI prolonged action potential duration in GH3 cells. With a minimal binding scheme, DPI-induced block of IK(DR) was quantitatively provided. The exposure to DPI also blocked IK(DR) with a concomitant increase in current inactivation in NG108-15 neuronal cells. Taken together, the results imply that DPI acts as an open-channel blocker of delayed-rectifier K+ channels in these cells. The widening of action potentials induced by DPI in these cells may be explained mainly by its block of IK(DR) in a state-dependent manner.

Original languageEnglish
Pages (from-to)409-423
Number of pages15
JournalJournal of Physiology and Pharmacology
Volume59
Issue number3
Publication statusPublished - 2008 Sept

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology

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