Characterization of a Palytoxin-Induced Non-selective Cation Channel in Mouse Megakaryocytes

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Author(s)

Abstract

We used the whole-cell clamp and fura-2 techniques to study the membrane current and intracellular Ca<SUP>2+</SUP> concentration ([Ca<SUP>2+</SUP>]<SUB>i</SUB>) changes of mouse megakaryocytes in response to palytoxin (PTX), a highly potent marine toxin. At a holding potential of -60 mV, PTX induced a sustained inward current in a dose-dependent manner. The reversal potentials measured in the presence of various extracellular major cations indicated that the PTX-induced channel had a non-selective permeability to alkali metal ions. Although elimination of intracellular Ca<SUP>2+</SUP> had no effect on the PTX-induced current, removal of external Ca<SUP>2+</SUP> inhibited the current activation. During the sustained phase of the PTX-induced current, treatment with ADP activated an additional current. Pretreatment with ouabain, an inhibitor of Na<SUP>+</SUP>-K<SUP>+</SUP>-ATPase, suppressed the PTX-induced current. During the stable phase of the PTX-induced current, challenge with NiCl<SUB>2</SUB> (5 mM) or 2, 4-dichlorobenzamil (DCB, 25 μM), a non-selective cation channel blocker, partially reversed the current. Simultaneous measurement of the membrane current and [Ca<SUP>2+</SUP>]<SUB>i</SUB> showed that PTX induced the current response without increasing the [Ca<SUP>2+</SUP>]<SUB>i</SUB>. Taken together, these results indicate that PTX induces a non-selective cation channel in mouse megakaryocytes. This channel is distinct from the ADP-operated channel and is sensitive to ouabain, NiCl<SUB>2</SUB> and DCB.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 81(2), 200-208, 1999-10

    The Japanese Pharmacological Society

References:  24

Codes

  • NII Article ID (NAID)
    10008196892
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4886681
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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