Chlorpromazine-induced changes in membrane micro-architecture inhibit thrombopoiesis in rat megakaryocytes

Itsuro Kazama, Yutaka Ejima, Yasuhiro Endo, Hiroaki Toyama, Mitsunobu Matsubara, Asuka Baba, Masahiro Tachi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Chlorpromazine often causes severe and persistent thrombocytopenia. Several clinical studies have suggested the presence of an as-yet-unknown mechanism in this drug-induced thrombocytopenia, by which the platelet production from megakaryocytes may directly be affected. As we previously demonstrated in rat peritoneal mast cells or adipocytes, chlorpromazine is amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membrane. Therefore, it can induce some structural changes in the megakaryocyte membrane surface and thus affect the process of thrombopoiesis. In the present study, employing the standard patch-clamp whole-cell recording technique, we examined the effects of chlorpromazine on the membrane capacitance and Kv1.3-channel currents in rat megakaryocytes. By electron microscopic imaging of the cellular surface, we also examined the effects of chlorpromazine on the membrane micro-architecture of megakaryocytes. Chlorpromazine markedly decreased the membrane capacitance of megakaryocytes, indicating the decreased number of invaginated plasma membranes, which was not detected by the fluorescent imaging techniques. As shown by electron microscopy, chlorpromazine actually changed the membrane micro-architecture of megakaryocytes, and was likely to halt the process of pro-platelet formation in the cells. This drug persistently decreased the membrane capacitance and almost totally and irreversibly inhibited the Kv1.3-channel currents in megakaryocytes. This study demonstrated for the first time that chlorpromazine is likely to inhibit the process of thrombopoiesis persistently in megakaryocytes, as detected by the long-lasting decrease in the membrane capacitance and the irreversible suppression of the Kv1.3-channel currents. Chlorpromazine-induced changes in the membrane micro-architecture are thought to be responsible for its persistent effects.

Original languageEnglish
Pages (from-to)2805-2812
Number of pages8
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1848
Issue number11
DOIs
Publication statusPublished - 2015 Nov 15

Keywords

  • Chlorpromazine
  • Megakaryocytes
  • Membrane capacitance
  • Membrane micro-architecture
  • Thrombopoiesis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Chlorpromazine-induced changes in membrane micro-architecture inhibit thrombopoiesis in rat megakaryocytes'. Together they form a unique fingerprint.

  • Cite this