title: Differential effects of clarithromycin and azithromycin 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 the channels play crucial roles in the lymphocyte activation and proliferation. Since macrolide antibiotics, such as clarithromycin and azithromycin, exert immunomodulatory effects, they would affect the Kv1.3-channel currents in lymphocytes.
  
  
  OBJECTIVE
  This study determined the physiological involvement in the mechanisms of immunomodulation by these antibiotics.
  
  
  METHODS
  Employing the standard patch-clamp whole-cell recording technique in murine thymocytes, we examined the effects of 30 and 100 µM clarithromycin and azithromycin on the Kv1.3-channel currents and the membrane capacitance.
  
  
  RESULTS
  Clarithromycin significantly suppressed the peak currents (30 µM, 178 ± 5.6 to 111 ± 2.0 pA/pF; 100 µM, 277 ± 4.4 to 89.6 ± 10 pA/pF) and the pulse-end currents (30 µM, 47.5 ± 2.2% to 15.5 ± 3.3%; 100 µM, 48.5 ± 1.4% to 15.8 ± 1.0%) of thymocyte Kv1.3-channels without significant effects on the membrane capacitance. In contrast, azithromycin did not affect the channel currents. However, it significantly decreased the membrane capacitance (30 µM, 4.68 ± 0.14 to 3.74 ± 0.13 pF; 100 µM, 4.47 ± 0.06 to 3.37 ± 0.08 pF), indicating its accumulation in the plasma membrane.
  
  
  CONCLUSIONS
  This study demonstrated for the first time that clarithromycin exerts inhibitory effects on thymocyte Kv1.3-channel currents, while azithromycin decreases the membrane capacitance without affecting the channel currents. These differences in the effects of the macrolide antibiotics may reflect differences in the mechanisms of immunomodulation by which they control the production of cytokines.
authors.affiliation: Department of Physiology I, Tohoku University Graduate School of Medicine, Miyagi, Japan. kazaitsu@med.tohoku.ac.jp
authors.forename: Itsuro
authors.initials: I
authors.lastname: Kazama
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017963:Azithromycin / Q000008:administration & dosage / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D017291:Clarithromycin / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology; D051664:Kv1.3 Potassium Channel / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D060168:Thymocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D007155:Immunologic Factors; D051664:Kv1.3 Potassium Channel; D017963:Azithromycin; D017291:Clarithromycin