Voltage-dependent biphasic effects of chloroquine on delayed rectifier K +-channel currents in murine thymocytes

I. Kazama, Y. Maruyama, Y. Murata, M. Sano

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Lymphocytes are of rich in delayed rectifier K +-channels (Kv1.3) in their plasma membranes, and the channels play crucial roles in the lymphocyte activation and proliferation. Since chloroquine, a widely used antimalarial drug, exerts immunosuppressive effects, it will affect the channel currents in lymphocytes. In the present study, employing the standard patch-clamp whole-cell recording technique, we examined the effects of chloroquine on the channels expressed in murine thymocytes. Published papers report that chloroquine will inhibit voltage-dependent K +-channel currents by plugging into the open-pore. We observed, indeed, that chloroquine suppressed the pulse-end currents of Kv1.3-channels at higher voltage steps. Surprisingly, however, we found that the drug enhanced the peak currents at both higher and lower voltage steps. Since chloroquine showed such biphasic effects on the thymocyte K +-channels, and since those effects were voltage dependent, we examined the effects of chloroquine on the activation and the inactivation of the channel currents. We noted that chloroquine shifted both the activation and the inactivation curves toward the hyperpolarizing potential, and that those shifts were more emphasized at lower voltage steps. We conclude that chloroquine facilitates both the activation and the inactivation of Kv1.3-channel currents in thymocytes, and that those effects are voltage dependent.

Original languageEnglish
Pages (from-to)267-274
Number of pages8
JournalJournal of Physiological Sciences
Volume62
Issue number3
DOIs
Publication statusPublished - 2012 May

Keywords

  • Activation
  • Chloroquine
  • Inactivation
  • Kv1.3-channel
  • Lymphocytes

ASJC Scopus subject areas

  • Physiology

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