Potassium channels mediate killing by human natural killer cells

Area of Science:

• Immunology
• Cell Biology
• Ion Channel Physiology

Background:

• Human natural killer (NK) cells eliminate various target cells.
• Ion channels were hypothesized to be involved in NK cell cytotoxicity, but direct evidence was lacking.
• Previous studies suggested a role for potassium (K+) and sodium (Na+) transport in target cells during cytotoxic T lymphocyte killing, a process resembling NK killing.

Purpose of the Study:

• To investigate the presence and function of ion channels in human NK cells and their target cells.
• To determine the role of identified ion channels in the cytotoxic activity of NK cells.

Main Methods:

• Whole-cell patch-clamp technique to identify ion currents in NK cells and target cells (K562, U937).
• Use of specific ion channel blockers (4-aminopyridine, quinidine, verapamil, Cd2+, tetrodotoxin) to assess their effects on ion currents and NK cell killing.
• Standard 51Cr-release assay to quantify NK cell-mediated target cell killing.

Main Results:

• A voltage-dependent potassium (K+) current was identified in human NK cells.
• This K+ current was inhibited by K+ channel blockers (4-aminopyridine, quinidine) and Ca2+ channel blockers (verapamil, Cd2+).
• Inhibition of NK cell K+ currents with these blockers dose-dependently reduced the killing of K562 and U937 target cells.
• Target cells (K562) exhibited a voltage-dependent Na+ current, but its blockade did not affect killing.
• No Ca2+ current was detected in either NK cells or target cells.

Conclusions:

• Potassium (K+) channels are present in human NK cells and play a necessary role in their cytotoxic function.
• The identified K+ channels in NK cells are crucial for the killing process.
• Endogenous ion channel types in target cells do not appear to be a primary factor in target cell susceptibility to NK cell-mediated lysis.