Extracellular K+ and Opening of Voltage-Gated Potassium Channels Activate T Cell Integrin Function: Physical and Functional Association between Kv1.3 Channels and β1 Integrins

摘要: Elevated extracellular K+ ([K+]o), in the absence of “classical” immunological stimulatory signals, was found to itself be a sufficient stimulus activate T cell β1 integrin moieties, and induce integrin-mediated adhesion migration. Gating voltage-gated channels (Kv1.3) appears crucial “decision-making” step, through which various physiological factors, including elevated [K+]o levels, affect function: opening channel leads function, whereas its blockage prevents it. In support this notion, we that proadhesive effects chemokine macrophage-inflammatory protein 1β, neuropeptide calcitonin gene–related peptide (CGRP), as well are blocked by specific Kv1.3 blockers, unique ability substance P inhibit correlates with inhibition. Interestingly, integrins coimmunoprecipitate, suggesting their physical association underlies functional cooperation on surface. This study shows cells can activated driven function pathway does not involve any receptors (i.e., [K+]o). addition, our results suggest undesired series pathological conditions arrested molecules block channels.