Activation of large-conductance Ca2+-activated K+ channels by pinacidil in human umbilical vascular endothelial cells

Sheng-Nan Wu, Hui Fang Li, Ai Yu Shen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The effect of pinacidil, an opener of ATP-sensitive K+ (K(ATP)) channels, on large-conductance Ca2+-activated K+ (BK(Ca)) channels was investigated in cultured endothelial cells of human umbilical veins. In whole cell configuration, pinacidil (30 μM) increased the amplitude of K+ outward currents (I(K)). Charybdotoxin (100 nM), but not glibenclamide (10 μM), suppressed pinacidil-induced increase in I(K). Neither carbonyl cyanide m- chlorophenyl hydrazone (CCCP; 10 μM), an inhibitor of mitochondrial Ca2+- uniporter, nor cyclosporin A (200 nM), an inhibitor of the mitochondrial permeability transition pore, affected pinacidil-induced increase in I(K). In inside-out patch configuration, bath application of pinacidil (30 μM) did not change single channel conductance but increased the activity of BK(Ca) channels. Pinacidil (30 μM) shifted the activation curve of BK(Ca) channels to less positive membrane potential by approximately 15 mV. Pinacidil stimulated the activity of these channels in a concentration-dependent manner. The EC50 value for pinacidil-induced channel activity was 20 μM. After BK(Ca) channels had been enhanced by Evans blue (100 μM), subsequent application of pinacidil (100 μM) did not further increase the channel activity. These results clearly indicate that in addition to the activation of K(ATP) channels, pinacidil can also stimulate BK(Ca) channels in endothelial cells. These effects could contribute to the regulation of vascular tone if similar results were found in endothelial cells in vivo.

Original languageEnglish
Pages (from-to)6-16
Number of pages11
JournalDrug Development Research
Volume48
Issue number1
DOIs
Publication statusPublished - 1999 Nov 10

Fingerprint

Pinacidil
Umbilicus
Calcium-Activated Potassium Channels
Endothelial Cells
Large-Conductance Calcium-Activated Potassium Channels
Carbonyl Cyanide m-Chlorophenyl Hydrazone
Adenosine Triphosphate
Charybdotoxin
Evans Blue
Umbilical Veins
Glyburide
Baths
Membrane Potentials
Cyclosporine
Blood Vessels
Cultured Cells

All Science Journal Classification (ASJC) codes

  • Drug Discovery

Cite this

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abstract = "The effect of pinacidil, an opener of ATP-sensitive K+ (K(ATP)) channels, on large-conductance Ca2+-activated K+ (BK(Ca)) channels was investigated in cultured endothelial cells of human umbilical veins. In whole cell configuration, pinacidil (30 μM) increased the amplitude of K+ outward currents (I(K)). Charybdotoxin (100 nM), but not glibenclamide (10 μM), suppressed pinacidil-induced increase in I(K). Neither carbonyl cyanide m- chlorophenyl hydrazone (CCCP; 10 μM), an inhibitor of mitochondrial Ca2+- uniporter, nor cyclosporin A (200 nM), an inhibitor of the mitochondrial permeability transition pore, affected pinacidil-induced increase in I(K). In inside-out patch configuration, bath application of pinacidil (30 μM) did not change single channel conductance but increased the activity of BK(Ca) channels. Pinacidil (30 μM) shifted the activation curve of BK(Ca) channels to less positive membrane potential by approximately 15 mV. Pinacidil stimulated the activity of these channels in a concentration-dependent manner. The EC50 value for pinacidil-induced channel activity was 20 μM. After BK(Ca) channels had been enhanced by Evans blue (100 μM), subsequent application of pinacidil (100 μM) did not further increase the channel activity. These results clearly indicate that in addition to the activation of K(ATP) channels, pinacidil can also stimulate BK(Ca) channels in endothelial cells. These effects could contribute to the regulation of vascular tone if similar results were found in endothelial cells in vivo.",
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Activation of large-conductance Ca2+-activated K+ channels by pinacidil in human umbilical vascular endothelial cells. / Wu, Sheng-Nan; Li, Hui Fang; Shen, Ai Yu.

In: Drug Development Research, Vol. 48, No. 1, 10.11.1999, p. 6-16.

Research output: Contribution to journalArticle

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