en P 44: The Role of HCN Channels in T Cell Function تحقیقات پایه در علوم اعصاب Basic research in Neuroscience پژوهشي Research --- Open Access, CC-BY-NC <table border="0" cellpadding="5px" cellspacing="2" dir="rtl" id="table_article" style="font-family: Tahoma; background-color: rgb(251, 250, 249); break-inside: avoid !important;" width="100%"> <tbody style="break-inside: avoid !important; font-size: 12px; margin-top: 0px; line-height: 2.2; margin-bottom: 0px; text-align: justify;"> <tr style="break-inside: avoid !important;"> <td class="abstractmed" colspan="2" style="break-inside: avoid !important;"> <p style="font-size: 12px; margin-top: 0px; margin-bottom: 0px; text-align: center;"><span style="color: rgb(0, 0, 0); font-size: 12px;">لطفاً به چکیده انگلیسی مراجعه شود.</span></p> </td> </tr> <tr style="break-inside: avoid !important;"> </tr> </tbody> </table> <p></p> <p>Ion channels play a major role in the regulation of T cell function in health and disease. In a computer-based model, established to simulate T cells&rsquo; membrane potential (V_M) generation, we discovered a discrepancy between the simulation and patch-clamp recordings. The predicted V_M was more hyperpolarized than the measured V_M, indicating that a yet unknown, depolarizing ion current might contribute to the T cells&rsquo; V_M. Since TASK2 and TASK3 channels are known to be expressed on T lymphocytes and the fact that the depolarizing I_h, mediated by HCN (hyperpolarization cyclic nucleotide activated) channels, was identified as a key antagonist of I_TASK in previous studies, HCN channels seem to be an ideal candidate to explain the discrepancy between measured and simulated V_M. HCN channels belong to the family of pore-loop ion channels and appear in four isoforms (HCN1-4) differing in activation kinetics, voltage and cAMP dependency and size. Their role for pacemaking activities in the heart and central nervous system is well known, however their expression and potential function in T cells has not been investigated so far and is subject to this study. In PCR and Western Blot experiments we could show the expression of HCN1-4 on T cells. HCN2 channels were upregulated upon stimulatory conditions both on mRNA and protein level. Quantification for HCN1 and HCN3-4 expression is currently pending. The pharmacological blockade of I_h by ivabradine (reversible) and ZD7288 (irreversible) resulted in differential, dose-dependent effects on cell viability and altered cytokine patterns as assessed by flow cytometry or ELISA respectively. Overall these findings support a regulatory role for HCN channels in T cell function and warrant further investigations.</p> Channels, Health, Disease 75 75 http://shefayekhatam.ir/browse.php?a_code=A-10-24-893&slc_lang=en&sid=1 Johannes Greiff Johannes Greiff johannes.greiff@gmail.com 100319475328460011952 100319475328460011952 Yes Universitätsklinikum Münster, Institut Für Translationale Neurologie, Münster, Germany Universitätsklinikum Münster, Institut Für Translationale Neurologie, Münster, Germany Lisa Epping Lisa Epping 100319475328460011953 100319475328460011953 No Universitätsklinikum Münster, Institut Für Translationale Neurologie, Münster, Germany Universitätsklinikum Münster, Institut Für Translationale Neurologie, Münster, Germany Tobias Ruck Tobias Ruck 100319475328460011954 100319475328460011954 No Universitätsklinikum Münster, Institut Für Translationale Neurologie, Münster, Germany Universitätsklinikum Münster, Institut Für Translationale Neurologie, Münster, Germany Julia Leonhardt Julia Leonhardt 100319475328460011955 100319475328460011955 No Universitätsklinikum Münster, Institut Für Translationale Neurologie, Münster, Germany Universitätsklinikum Münster, Institut Für Translationale Neurologie, Münster, Germany Sven G Meuth Sven G Meuth 100319475328460011956 100319475328460011956 No Universitätsklinikum Münster, Institut Für Translationale Neurologie, Münster, Germany Universitätsklinikum Münster, Institut Für Translationale Neurologie, Münster, Germany