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Development of a delayed outward-rectifying K+ conductance in cultured mouse peritoneal macrophages
Abstract:
Patch clamp techniques were used to study ionic currents in cultured mouse peritoneal macrophages. Whole-cell voltage clamp studies of cells 1-5 hr after isolation showed only a high-resistance linear membrane. After 1 day in culture, 82 of 85 cells studied had developed a voltage- and time-dependent potassium (K+) conductance similar to the delayed outward rectifier in nerve and muscle cells. The current activated when the membrane was depolarized above -50 mV. The sigmoidally rising current rose to a peak at a rate that increased with depolarization. Inactivation proceeded exponentially with a time constant of approximately equal to 450 ms. Recovery from inactivation was slow (tau = 12 s). The reversal potentials for varying extracellular K+ concentrations followed the Nernst predictions for a K+ -specific channel. The conductance was blocked by extracellular 4-aminopyridine and by intracellular tetraethylammonium chloride, barium, and cesium. Single-channel K+ currents comprising this net current had a conductance of 16 pS, exhibited bursting behavior, and inactivated with time. No inward currents were ever detected in macrophages cultivated for up to 4 days. Short-term exposure to chemoattractant and transmitter agents failed to activate an inward current. Macrophages may change their membrane electrophysiological properties depending on their state of functional activation. We postulate that the K+ conductance develops prior to depolarizing conductances involved in the macrophage's immunological functions.
Insights
Cultured mouse macrophages develop a potassium (K+) conductance, crucial for their function. This ion channel activity appears before other electrical changes needed for immune responses.
Area of Science:
- Cellular Electrophysiology
- Immunology
- Ion Channel Biology
Background:
- Macrophages are key immune cells.
- Their electrophysiological properties are not fully understood.
- Understanding macrophage ion channels is vital for immunology.
Purpose of the Study:
- To investigate ionic currents in cultured mouse peritoneal macrophages.
- To characterize the development and properties of potassium (K+) conductance.
- To explore potential roles in macrophage activation.
Main Methods:
- Patch clamp techniques, including whole-cell voltage clamp.
- Studies on macrophages cultured for 1-4 days.
- Investigation of single-channel K+ currents.
Main Results:
- Macrophages developed voltage- and time-dependent K+ conductance after 1 day in culture.
- This conductance resembled the delayed outward rectifier found in nerve and muscle cells.
- Single-channel analysis revealed K+ currents with specific conductance and inactivation properties.
Conclusions:
- Cultured macrophages develop a significant K+ conductance.
- This K+ conductance may precede other electrical changes in macrophage activation.
- Electrophysiological properties of macrophages can change with their functional state.