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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

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Ion-channel activities regulate transmembrane signaling in thymocyte apoptosis and T-cell activation

P Nagy1, G Panyi, A Jenei

  • 1Department of Biophysics, University Medical School of Debrecen, Hungary.

Immunology Letters
|January 1, 1995
PubMed

Insights

Ion channels significantly impact lymphocyte apoptosis sensitivity. Thymocyte maturation affects responses to extracellular ATP, while lymphoma cells show resistance, highlighting the role of ion channel activity in T-lymphocyte proliferation.

Area of Science:

  • Immunology
  • Cell Biology
  • Biophysics

Background:

  • Plasma membrane ion channels, including calcium (Ca2+) and potassium (K+) channels, are recognized for their roles in lymphocyte activation and thymocyte apoptosis.
  • Understanding the specific contribution of these ion channels to apoptosis sensitivity in lymphoid cells is crucial.

Purpose of the Study:

  • To investigate the role of ion channels in the sensitivity and resistance of lymphoid cells to extracellular ATP (ATPex)-induced apoptosis.
  • To explore the influence of maturation and differentiation states on ATPex-induced apoptosis in thymocytes and lymphoma cell lines.
  • To examine the effect of bretylium tosylate, a K+ channel blocker, on T-lymphocyte proliferation and ion channel activity.

Main Methods:

  • Utilized extracellular ATP (ATPex) to induce apoptosis in thymocytes and human lymphoma cell lines.
  • Measured intracellular calcium levels and membrane permeability in response to ATPex.
  • Employed patch-clamp techniques to analyze single-channel properties and whole-cell currents of voltage-gated K+ channels.

Main Results:

  • Thymocytes exhibited sensitivity to ATPex, characterized by immediate intracellular calcium increases and subsequent membrane permeability changes.
  • Mature (medullary) thymocytes were more sensitive to ATPex than cortical thymocytes.
  • Human lymphoma cell lines, including SUPT13, demonstrated high resistance to ATPex-induced apoptosis.
  • Bretylium tosylate was shown to depress whole-cell K+ currents and influence single-channel properties of voltage-gated K+ channels.

Conclusions:

  • Lymphoid cell apoptosis sensitivity to extracellular ATP is dependent on maturation/differentiation state, likely due to alterations in ATP-receptor signaling pathways and associated ion channels.
  • K+ channel activity plays a critical role in T-lymphocyte proliferation, as evidenced by the effects of bretylium tosylate.

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