title: Suppressive effects of diltiazem and verapamil on delayed rectifier K(+)-channel currents in murine thymocytes.
abstract: BACKGROUND
  Lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes, and these channels play crucial roles in the lymphocyte activation and proliferation. Since diltiazem and verapamil, which are highly lipophilic Ca(2+) channel blockers (CCBs), exert relatively stronger immunomodulatory effects than the other types of CCBs, they would affect the Kv1.3-channel currents in lymphocytes.
  
  
  METHODS
  Employing the standard patch-clamp whole-cell recording technique in murine thymocytes, we examined the effects of these drugs on the channel currents and the membrane capacitance.
  
  
  RESULTS
  Both diltiazem and verapamil significantly suppressed the peak and the pulse-end currents of the channels, although the effects of verapamil were more marked than those of diltiazem. Both drugs significantly lowered the membrane capacitance, indicating the interactions between the drugs and the plasma membranes.
  
  
  CONCLUSIONS
  This study demonstrated for the first time that CCBs, such as diltiazem and verapamil, exert inhibitory effects on Kv1.3-channels expressed in lymphocytes. The effects of these drugs may be associated with the mechanisms of immunomodulation by which they decrease the production of inflammatory cytokines.
authors.affiliation: Department of Physiology I, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Baba
authors.affiliation: Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tachi
authors.affiliation: Department of Physiology I, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Maruyama
authors.affiliation: Department of Physiology I, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: kazaitsu@med.tohoku.ac.jp.
authors.forename: Itsuro
authors.initials: I
authors.lastname: Kazama
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology*; D051664:Kv1.3 Potassium Channel / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018408:Patch-Clamp Techniques; D060168:Thymocytes / Q000187:drug effects* / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D051668:Delayed Rectifier Potassium Channels; C496974:Kcna3 protein, mouse; D051664:Kv1.3 Potassium Channel; D014700:Verapamil; D004110:Diltiazem
keywords: Diltiazem; Immunosuppressive effects; Kv1.3-channel; Membrane capacitance; Verapamil