Kv1.3 Current Voltage Dependence in Lymphocytes is Modulated by Co-Culture with Bone Marrow-Derived Stromal Cells: B and T Cells Respond Differentially

Cell Physiol Biochem. 2020 Sep 5;54(5):842-852. doi: 10.33594/000000273.

Abstract

Background/aims: Kv1.3 channel is the only voltage-dependent potassium channel in plasma membrane of human lymphocytes. Bearing in mind a rather steep voltage-dependence of Kv1.3 activation and inactivation, its modulation by B and T cells activation and by co-culture with stromal bone-marrow cells was addressed.

Methods: Patch-clamp technique in the whole cell mode was applied to human resting and activated human B and T cells, in monoculture and co-culture with stromal OP9 cells.

Results: Polyclonal activation of B and T cells in monoculture caused Kv1.3 current in B cells to activate at more negative and in T cells at more positive potentials, whereas the inactivation of Kv1.3 current in resting T cells occurred at more negative voltages. Co-culture with OP9 cells abolished the shift of voltage dependence upon the polyclonal activation but fixed the substantial difference between B and T cells, resting or activated, with both activation and inactivation negatively shifted by 15 mV for T lymphocytes. However, activated B cells displayed an incomplete inactivation, which was augmented by the co-culture. Neither activation nor co-culture caused substantial changes in the Kv1.3 current density.

Conclusion: The combination of activation and inactivation processes yields the fraction of steady-state Kv1.3 current (window current), which was higher in activated B cells, partly due to an incomplete inactivation. A relatively smaller window current in resting B cells and resting T cells in co-culture correlated with a more depolarized resting membrane potential. Rather than insignificant changes in the Kv1.3 channels functional expression, the modulation of their voltage dependence by activation and co-culture with bone-marrow stromal cells was essential for the control of membrane potential.

Keywords: Kv1.3 channel; Voltage dependence; B lymphocytes; T lymphocytes; Mesenchymal stem cells.

MeSH terms

  • Adult
  • B-Lymphocytes / metabolism*
  • Bone Marrow / metabolism
  • Coculture Techniques
  • Female
  • Healthy Volunteers
  • Humans
  • Ion Channel Gating / physiology
  • Kv1.3 Potassium Channel / metabolism*
  • Kv1.3 Potassium Channel / physiology
  • Lymphocyte Activation / physiology
  • Lymphocytes / metabolism
  • Male
  • Membrane Potentials / physiology
  • Patch-Clamp Techniques
  • Stromal Cells / metabolism
  • T-Lymphocytes / metabolism*

Substances

  • Kv1.3 Potassium Channel