Referenced in: none

Automatically associated channels: Kv1.1 , Kv1.2 , Kv1.3 , Kv1.6

Title: Modulation of Kv channel expression and function by TCR and costimulatory signals during peripheral CD4(+) lymphocyte differentiation.

Authors: Qing-Hua Liu, Bernd K Fleischmann, Brian Hondowicz, Curtis C Maier, Laurence A Turka, Katsuyuki Yui, Michael I Kotlikoff, Andrew D Wells, Bruce D Freedman

Journal, date & volume: J. Exp. Med., 2002 Oct 7 , 196, 897-909

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12370252

Abstract
Ionic signaling pathways, including voltage-dependent potassium (Kv) channels, are instrumental in antigen-mediated responses of peripheral T cells. However, how Kv channels cooperate with other signaling pathways involved in T cell activation and differentiation is unknown. We report that multiple Kv channels are expressed by naive CD4(+) lymphocytes, and that the current amplitude and kinetics are modulated by antigen receptor-mediated stimulation and costimulatory signals. Currents expressed in naive CD4(+) lymphocytes are consistent with Kv1.1, Kv1.2, Kv1.3, and Kv1.6. Effector CD4(+) cells generated by optimal TCR and costimulation exhibit only Kv1.3 current, but at approximately sixfold higher levels than naive cells. CD4(+) lymphocytes anergized through partial stimulation exhibit similar Kv1.1, Kv1.2, and/or Kv1.6 currents, but approximately threefold more Kv1.3 current than naive cells. To determine if Kv channels contribute to the distinct functions of naive, effector, and anergized T cells, we tested their role in immunoregulatory cytokine production. Each Kv channel is required for maximal IL-2 production by naive CD4(+) lymphocytes, whereas none appears to play a role in IL-2, IL-4, or IFN-gamma production by effector cells. Interestingly, Kv channels in anergized lymphocytes actively suppress IL-4 production, and these functions are consistent with a role in regulating the membrane potential and calcium signaling.