TY - JOUR
T1 - Pharmacological and molecular characterization of ATP-sensitive K+ channels in the TE671 human medulloblastoma cell line
AU - Miller, Thomas R.
AU - Taber, Rachel Davis
AU - Molinari, Eduardo J.
AU - Whiteaker, Kristi L.
AU - Monteggia, Lisa M
AU - Scott, Victoria E S
AU - Brioni, Jorge D.
AU - Sullivan, James P.
AU - Gopalakrishnan, Murali
PY - 1999/4/9
Y1 - 1999/4/9
N2 - ATP-sensitive K+ (K(ATP)) channels in the human medulloblastoma TE671 cell line were characterized by membrane potential assays utilizing a potentiometric fluorescent probe, bis-(1,3-dibutylbarbituric acid)trimethine oxonol (DiBAC4(3)), and by mRNA analysis. Membrane potential assays showed concentration-dependent and glyburide-sensitive changes in fluorescence upon addition of (-)-cromakalim, pinacidil, diazoxide and P1075. The rank order of potency for these openers was P1075>(-)-cromakalim~pinacidil>diazoxide. Additionally, glyburide and glipizide inhibited P1075-evoked responses in TE671 cells with half-maximal inhibitory concentrations of 0.22 and 14 μM, respectively. The rank order potencies of both openers and inhibitors were similar to those observed in the rat smooth muscle A-10 cell line. In contrast, in the rat pancreatic insulinoma RIN-m5F cell line, only diazoxide was effective as an opener. Reverse transcription-polymerase chain reaction (RT-PCR) studies detected sulfonylurea receptors SUR2B and SUR1 mRNA in TE671 cells whereas only SUR2B and SUR1 mRNA were, respectively, detected in A-10 and RIN-m5F cells. The inward rectifier Kir6.2 mRNA was detected in all three cell types whereas Kir6.1 was detected only in A-10 cells. Collectively, the molecular and pharmacologic studies suggest that K(ATP) channels endogenously expressed in TE671 medulloblastoma resemble those present in the smooth muscle. Copyright (C) 1999 Elsevier Science B.V.
AB - ATP-sensitive K+ (K(ATP)) channels in the human medulloblastoma TE671 cell line were characterized by membrane potential assays utilizing a potentiometric fluorescent probe, bis-(1,3-dibutylbarbituric acid)trimethine oxonol (DiBAC4(3)), and by mRNA analysis. Membrane potential assays showed concentration-dependent and glyburide-sensitive changes in fluorescence upon addition of (-)-cromakalim, pinacidil, diazoxide and P1075. The rank order of potency for these openers was P1075>(-)-cromakalim~pinacidil>diazoxide. Additionally, glyburide and glipizide inhibited P1075-evoked responses in TE671 cells with half-maximal inhibitory concentrations of 0.22 and 14 μM, respectively. The rank order potencies of both openers and inhibitors were similar to those observed in the rat smooth muscle A-10 cell line. In contrast, in the rat pancreatic insulinoma RIN-m5F cell line, only diazoxide was effective as an opener. Reverse transcription-polymerase chain reaction (RT-PCR) studies detected sulfonylurea receptors SUR2B and SUR1 mRNA in TE671 cells whereas only SUR2B and SUR1 mRNA were, respectively, detected in A-10 and RIN-m5F cells. The inward rectifier Kir6.2 mRNA was detected in all three cell types whereas Kir6.1 was detected only in A-10 cells. Collectively, the molecular and pharmacologic studies suggest that K(ATP) channels endogenously expressed in TE671 medulloblastoma resemble those present in the smooth muscle. Copyright (C) 1999 Elsevier Science B.V.
KW - Glyburide
KW - K channel, ATP-sensitive
KW - K channel, inward rectifying
KW - Sulfonylurea receptor
KW - TE671 medulloblastoma cell
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U2 - 10.1016/S0014-2999(99)00128-4
DO - 10.1016/S0014-2999(99)00128-4
M3 - Article
C2 - 10323267
AN - SCOPUS:0033007854
SN - 0014-2999
VL - 370
SP - 179
EP - 185
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -