Transmembrane potential responses during HL-60 promyelocyte differentiation.
Myeloid cells, including granulocytes and monocyte/macrophages, are important in disease-associated inflammatory reactions. These cells come from a common progenitor, the promyelocyte. The human promyelocytic cell line, HL-60, can be induced to terminally differentiate into granulocytes or monocyte/ macrophages in a controlled fashion providing a model to study various aspects of myelomonocytic differentiation. The expression of several ion channels is controlled in HL-60 cells in a differentiation specific pattern. The purpose of this study was to determine if lineage-specific ion channel expression during HL-60 differentiation resulted in differences in functional responses to external stimuli. This was investigated by examining transmembrane potential responses in HL-60 promyelocytes, HL-60-derived polymorphonuclear cells (PMNs), and monocytes to various stimuli using the transmembrane potential sensitive dye, diSBAC2-(3). Exposure of HL-60 promyelocytes to ionomycin or ATP produced a membrane hyperpolarization. Studies using ion substitutions and ion channel blockers indicate that the hyperpolarization was mediated by KCa channels. During HL-60 promyelocyte differentiation to PMNs, the membrane potential response to ionomycin and ATP shifted from a hyperpolarization to a depolarization over 7 days. Conversely, HL-60-derived monocytes exhibited a membrane hyperpolarization in response to ionomycin and ATP. HL-60-derived monocytes also exhibit a Cl- conductance specifically induced by ATP. Lineage-specific expression of ion channels during HL-60 cell differentiation is important in determining the transmembrane potential response of these cells. This may be translated into functional responses of various myelomonocytic cells during disease-associated inflammatory reactions.
Brent
L H
LH
Department of Medicine, Hahnemann University, Philadelphia, Pennsylvania 19102, USA.
Rubenstein
B
B
Gong
Q H
QH
Wieland
S J
SJ
D002118:Calcium / Q000502:physiology; D002454:Cell Differentiation; D018922:HL-60 Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D011188:Potassium / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*
D008934:Mitogens; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011188:Potassium; D002118:Calcium