TY - JOUR
T1 - Role of K+ channel expression in polyamine-dependent intestinal epithelial cell migration
AU - Wang, Jian Ying
AU - Wang, Jian
AU - Golovina, Vera A.
AU - Li, L. I.
AU - Platoshyn, Oleksandr
AU - Yuan, Jason Xiao Jian
PY - 2000
Y1 - 2000
N2 - Polyamines are essential for cell migration during early mucosal restitution after wounding in the gastrointestinal tract. Activity of voltage-gated K+ channels (Kv) controls membrane potential (E(m)) that regulates cytoplasmic free Ca2+ concentration ([Ca2+](cyt)) by governing the driving force for Ca2+ influx. This study determined whether polyamines are required for the stimulation of cell migration by altering K+ channel gene expression, E(m), and [Ca2+](cyt) in intestinal epithelial cells (IEC-6). The specific inhibitor of polyamine synthesis, α- difluoromethylornithine (DFMO, 5 mM), depleted cellular polyamines (putrescine, spermidine, and spermine), selectively inhibited Kv1.1 channel (a delayed-rectifier Kv channel) expression, and resulted in membrane depolarization. Because IEC-6 cells did not express voltage-gated Ca2+ channels, the depolarized E(m) in DFMO-treated cells decreased [Ca2+](cyt) as a result of reduced driving force for Ca2+ influx through capacitative Ca2+ entry. Migration was reduced by 80% in the polyamine-deficient cells. Exogenous spermidine not only reversed the effects of DFMO on Kv1.1 channel expression, E(m), and [Ca2+](cyt) but also restored cell migration to normal. Removal of extracellular Ca2+ or blockade of Kv channels (by 4- aminopyridine, 1-5 mM) significantly inhibited normal cell migration and prevented the restoration of cell migration by exogenous spermidine in polyamine-deficient cells. These results suggest that polyamine-dependent intestinal epithelial cell migration may be due partially to an increase of Kv1.1 channel expression. The subsequent membrane hyperpolarization raises [Ca2+](cyt) by increasing the driving force (the electrochemical gradient) for Ca2+ influx and thus stimulates cell migration.
AB - Polyamines are essential for cell migration during early mucosal restitution after wounding in the gastrointestinal tract. Activity of voltage-gated K+ channels (Kv) controls membrane potential (E(m)) that regulates cytoplasmic free Ca2+ concentration ([Ca2+](cyt)) by governing the driving force for Ca2+ influx. This study determined whether polyamines are required for the stimulation of cell migration by altering K+ channel gene expression, E(m), and [Ca2+](cyt) in intestinal epithelial cells (IEC-6). The specific inhibitor of polyamine synthesis, α- difluoromethylornithine (DFMO, 5 mM), depleted cellular polyamines (putrescine, spermidine, and spermine), selectively inhibited Kv1.1 channel (a delayed-rectifier Kv channel) expression, and resulted in membrane depolarization. Because IEC-6 cells did not express voltage-gated Ca2+ channels, the depolarized E(m) in DFMO-treated cells decreased [Ca2+](cyt) as a result of reduced driving force for Ca2+ influx through capacitative Ca2+ entry. Migration was reduced by 80% in the polyamine-deficient cells. Exogenous spermidine not only reversed the effects of DFMO on Kv1.1 channel expression, E(m), and [Ca2+](cyt) but also restored cell migration to normal. Removal of extracellular Ca2+ or blockade of Kv channels (by 4- aminopyridine, 1-5 mM) significantly inhibited normal cell migration and prevented the restoration of cell migration by exogenous spermidine in polyamine-deficient cells. These results suggest that polyamine-dependent intestinal epithelial cell migration may be due partially to an increase of Kv1.1 channel expression. The subsequent membrane hyperpolarization raises [Ca2+](cyt) by increasing the driving force (the electrochemical gradient) for Ca2+ influx and thus stimulates cell migration.
KW - Intestinal epithelial cells
KW - Intracellular calcium
KW - Membrane potential
KW - Polyamines
KW - Voltage-gated potassium channels
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U2 - 10.1152/ajpcell.2000.278.2.c303
DO - 10.1152/ajpcell.2000.278.2.c303
M3 - Article
C2 - 10666025
AN - SCOPUS:0034011333
SN - 0363-6143
VL - 278
SP - C303-C314
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 2 47-2
ER -