TY - JOUR
T1 - Extracellular K+ and opening of voltage-gated potassium channels activate T cell integrin function
T2 - Physical and functional association between Kv1.3 channels and β1 integrins
AU - Levite, Mia
AU - Cahalon, Liora
AU - Peretz, Asher
AU - Hershkoviz, Rami
AU - Sobko, Alex
AU - Ariel, Amiram
AU - Desai, Rooma
AU - Attali, Bernard
AU - Lider, Ofer
PY - 2000/4/3
Y1 - 2000/4/3
N2 - Elevated extracellular K+ ([K+](o)), in the absence of 'classical' immunological stimulatory signals, was found to itself be a sufficient stimulus to activate T cell β1 integrin moieties, and to induce integrin- mediated adhesion and migration. Gating of T cell voltage-gated K+ channels (Kv1.3) appears to be the crucial 'decision-making' step, through which various physiological factors, including elevated [K+](o) levels, affect the T cell β1 integrin function: opening of the channel leads to function, whereas its blockage prevents it. In support of this notion, we found that the proadhesive effects of the chemokine macrophage-inflammatory protein 1β, the neuropeptide calcitonin gene-related peptide (CGRP), as well as elevated [K+](o) levels, are blocked by specific Kv1.3 channel blockers, and that the unique physiological ability of substance P to inhibit T cell adhesion correlates with Kv1.3 inhibition. Interestingly, the Kv1.3 channels and the β1 integrins coimmunoprecipitate, suggesting that their physical association underlies their functional cooperation on the T cell surface. This study shows that T cells can be activated and driven to integrin function by a pathway that does not involve any of its specific receptors (i.e., by elevated [K+](o)). In addition, our results suggest that undesired T cell integrin function in a series of pathological conditions can be arrested by molecules that block the Kv1.3 channels.
AB - Elevated extracellular K+ ([K+](o)), in the absence of 'classical' immunological stimulatory signals, was found to itself be a sufficient stimulus to activate T cell β1 integrin moieties, and to induce integrin- mediated adhesion and migration. Gating of T cell voltage-gated K+ channels (Kv1.3) appears to be the crucial 'decision-making' step, through which various physiological factors, including elevated [K+](o) levels, affect the T cell β1 integrin function: opening of the channel leads to function, whereas its blockage prevents it. In support of this notion, we found that the proadhesive effects of the chemokine macrophage-inflammatory protein 1β, the neuropeptide calcitonin gene-related peptide (CGRP), as well as elevated [K+](o) levels, are blocked by specific Kv1.3 channel blockers, and that the unique physiological ability of substance P to inhibit T cell adhesion correlates with Kv1.3 inhibition. Interestingly, the Kv1.3 channels and the β1 integrins coimmunoprecipitate, suggesting that their physical association underlies their functional cooperation on the T cell surface. This study shows that T cells can be activated and driven to integrin function by a pathway that does not involve any of its specific receptors (i.e., by elevated [K+](o)). In addition, our results suggest that undesired T cell integrin function in a series of pathological conditions can be arrested by molecules that block the Kv1.3 channels.
KW - Extracellular K
KW - Integrins
KW - Neuroimmunomodulation
KW - Potassium channels
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=0034600069&partnerID=8YFLogxK
U2 - 10.1084/jem.191.7.1167
DO - 10.1084/jem.191.7.1167
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C2 - 10748234
AN - SCOPUS:0034600069
SN - 0022-1007
VL - 191
SP - 1167
EP - 1176
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 7
ER -