Kv1.3/Kv1.5 heteromeric channels compromise pharmacological responses in macrophages.
Voltage-dependent K(+) (Kv) channels are involved in the immune response. Kv1.3 is highly expressed in activated macrophages and T-effector memory cells of autoimmune disease patients. Macrophages are actively involved in T-cell activation by cytokine production and antigen presentation. However, unlike T-cells, macrophages express Kv1.5, which is resistant to Kv1.3-drugs. We demonstrate that mononuclear phagocytes express different Kv1.3/Kv1.5 ratios, leading to biophysically and pharmacologically distinct channels. Therefore, Kv1.3-based treatments to alter physiological responses, such as proliferation and activation, are impaired by Kv1.5 expression. The presence of Kv1.5 in the macrophagic lineage should be taken into account when designing Kv1.3-based therapies.
Villalonga
Núria
N
Molecular Physiology Laboratory, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Avda. Diagonal 645, E-08028 Barcelona, Spain.
Escalada
Artur
A
Vicente
Rubén
R
Sánchez-Tilló
Ester
E
Celada
Antonio
A
Solsona
Carles
C
Felipe
Antonio
A
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002478:Cells, Cultured; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D051666:Kv1.5 Potassium Channel / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D012604:Scorpion Venoms / Q000494:pharmacology
D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel; D012604:Scorpion Venoms; C077910:margatoxin