Compensatory anion currents in Kv1.3 channel-deficient thymocytes.
Kv1.3 is a voltage-gated potassium channel with roles in human T cell activation/proliferation, cell-mediated cytotoxicity, and volume regulation and is thus a target for therapeutic control of T cell responses. Kv1.3 is also present in some mouse thymocyte subsets and splenocytes, but its role in the mouse is less well understood. We report the generation and characterization of Kv1.3-deficient (Kv1.3-/-) mice. In contrast to wild-type cells, the majority of Kv1.3-/- thymocytes had no detectable voltage-dependent potassium current, although RNA and protein for several potassium channel subunits were found in the thymocyte population. Surprisingly, the level of chloride current in the Kv1.3-/- thymocytes was increased approximately 50-fold over that in wild-type cells. There were no abnormalities in lymphocyte types or absolute numbers in thymus, spleen, and lymph nodes and no obvious defect in thymocyte apoptosis or T cell proliferation in the Kv1.3-/- animals. The compensatory effects of the enhanced chloride current may account for the apparent lack of immune system defects in Kv1.3-/-mice.
Koni
Pandelakis A
PA
Section of Immunobiology,, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Khanna
Rajesh
R
Chang
Martin C
MC
Tang
Michael D
MD
Kaczmarek
Leonard K
LK
Schlichter
Lyanne C
LC
Flavella
Richard A
RA
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002455:Cell Division; D018118:Chloride Channels / Q000378:metabolism; D004247:DNA / Q000235:genetics; D005260:Female; D015870:Gene Expression; D017136:Ion Transport; D051664:Kv1.3 Potassium Channel; D008213:Lymphocyte Activation; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D018118:Chloride Channels; C496974:Kcna3 protein, mouse; D051664:Kv1.3 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D004247:DNA