Induction of calcium-activated potassium channel activity by hemin in human erythroleukemia cells.
The agent hemin has been demonstrated to be able to initiate a coordinated differentiation program in several cell types. In the present study, we examined the ability of hemin on inducing cell differentiation and Ca(2+)-activated K(+) channel activity in erythroleukemic K562 cells. Treating undifferentiated K562 cells with hemin (0.1 mM) for five days caused these cells to display differentiation-like characteristics including chromatin aggregation, nuclear degradation, pseudopod extension of the membrane and increased hemoglobin production. However, overall cell viability was not significantly changed by the presence of hemin. After hemin treatment for different periods, the Ca(2+)-activated K(+) channel was activated by the addition of ionomycin (1 microM), and was inhibited by either clotrimazole, charybdotoxin, or EGTA. Before hemin treatment there was no significant Ca(2+)-activated K(+) channel activity present in undifferentiated K562 cells. After hemin treatment for 5 days, a significant Ca(2+)-activated K(+) channel activity was detected. This increasing Ca(2+)-activated K(+) channel activity may be contributed from a subtype of Ca(2+)-activated K(+) channel, KCNN4. These results suggest that the ability of hemin to induce increasing Ca(2+)-activated K(+) channel activity may contribute to the mechanism of hemin-induced K562 cell differentiation.
Huang
Chiun-Chien
CC
Department of Physiology, Chung Shan Medical University, Taichung 40203, Taiwan, ROC. huanglim@ms71.hinet.net
Hall
Andrew C
AC
Lim
Poh-Hong
PH
D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002454:Cell Differentiation; D002470:Cell Survival; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects*
D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D006427:Hemin; D002118:Calcium