Ca(2+)-insensitive modulation of a K+ conductance by inositol polyphosphates
1Department of Anatomy, Hahnemann University, Philadelphia, Pennsylvania 19102.
The Journal of Biological Chemistry
|August 15, 1991
Summary
Inwardly rectifying potassium channels in human macrophages are modulated by inositol polyphosphates, particularly IP4. These findings reveal a novel cellular function for inositol polyphosphates in regulating macrophage ion channel activity.
Area of Science:
- Cellular Physiology
- Immunology
- Molecular Biology
Background:
- Human leukemic (HL-60) cell-derived macrophages possess voltage-activated inward rectifying potassium conductance.
- Macrophage colony-stimulating factor modulates this potassium conductance.
Purpose of the Study:
- Investigate the roles of intracellular messengers in the regulation of macrophage inward rectifying potassium conductance.
- Determine the specific signaling pathways involved in the modulation of this ion channel.
Main Methods:
- Utilized tight-seal whole-cell recording techniques on HL-60 cell-derived macrophages.
- Employed intracellular dialysis with various signaling molecules, including inositol 1,3,4,5-tetrakisphosphate (IP4), inositol 1,4,5-trisphosphate, and guanosine 5'-O-(thiotriphosphate) (GTPγS).
- Monitored changes in voltage-activated inward rectifying potassium conductance.
Main Results:
- Intracellular dialysis with IP4 or inositol 1,4,5-trisphosphate rapidly increased the inward rectifying conductance.
- Changes in intracellular calcium levels alone did not replicate the stimulatory effect.
- Dialysis with GTPγS resulted in significant inhibition of the potassium conductance.
Conclusions:
- Inositol polyphosphates, especially IP4, play a novel cellular role in regulating macrophage ion channel activity.
- Demonstrated an antagonistic modulation of the human macrophage inward rectifier by IP4 and GTPγS.
- Suggests a complex intracellular signaling network involving inositol phosphates and G-proteins in macrophage potassium channel regulation.
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