The mechanism of actions of 3-(5'-(hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) on Ca2+-activated K+ currents in GH3 lactotrophs

Sheng-Nan Wu, Tsong Long Hwang, Che Ming Teng, Hui Fang Li, Chung Ren Jan

Research output: Contribution to journalArticle

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Abstract

The effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), an activator of soluble guanylyl cyclase, on ionic currents have been assessed in rat pituitary GH3 lactotrophs. In GH3 cells bathed in normal Tyrode's solution, YC-1 (1 μM) reversibly suppressed the amplitude of the Ca2+-activated K+ current (I(K(Ca))). YC-1 at a concentration above 10 μM produced a biphasic response in the amplitude of I(K(Ca)), i.e., an initial decrease followed by a sustained increase. When the pipette solutions were filled with high EGTA (10 mM), the YC-1-induced stimulatory effect on I(K(Ca)) was abolished. Over a similar concentration range, YC-1 also effectively inhibited the voltage-dependent K+ current (I(K(V))) in GH3 cells. The IC50 value required for the inhibition of I(K(V)) by YC-1 was 1 μM. Unlike YC-1, 8-bromo cGMP did not inhibit I(K(Ca)). However, YC-1 (10 μM) did not affect the amplitude of L-type Ca2+ current. In the cell-attached configuration, application of YC-1 (10 μM) to the bath did not change the single-channel conductance of the large-conductance Ca2+-activated K+ (BK(Ca)) channels; however, it did increase the opening probability of BK(Ca) channels. In contrast, in the outside-out configuration, YC-1 (10 μM) significantly suppressed the opening probability of BK(Ca) channels. The present study shows dual effects of YC-1 on I(K(Ca)) in GH3 cells. The YC-1-mediated stimulation of I(K(Ca)) may result from elevated cytosolic Ca2+, whereas the inhibition of I(K(Ca)) and I(K(V)) by YC-1 appears to be direct and independent of the activation of soluble guanylyl cyclase. Caution thus needs to be used in attributing the YC-1-mediated response to the activation of soluble guanylyl cyclase. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)1788-1799
Number of pages12
JournalNeuropharmacology
Volume39
Issue number10
DOIs
Publication statusPublished - 2000 Sep 1

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Indazoles
Lactotrophs
Large-Conductance Calcium-Activated Potassium Channels
Egtazic Acid
Baths
Inhibitory Concentration 50
Soluble Guanylyl Cyclase

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Wu, Sheng-Nan ; Hwang, Tsong Long ; Teng, Che Ming ; Li, Hui Fang ; Jan, Chung Ren. / The mechanism of actions of 3-(5'-(hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) on Ca2+-activated K+ currents in GH3 lactotrophs. In: Neuropharmacology. 2000 ; Vol. 39, No. 10. pp. 1788-1799.
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abstract = "The effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), an activator of soluble guanylyl cyclase, on ionic currents have been assessed in rat pituitary GH3 lactotrophs. In GH3 cells bathed in normal Tyrode's solution, YC-1 (1 μM) reversibly suppressed the amplitude of the Ca2+-activated K+ current (I(K(Ca))). YC-1 at a concentration above 10 μM produced a biphasic response in the amplitude of I(K(Ca)), i.e., an initial decrease followed by a sustained increase. When the pipette solutions were filled with high EGTA (10 mM), the YC-1-induced stimulatory effect on I(K(Ca)) was abolished. Over a similar concentration range, YC-1 also effectively inhibited the voltage-dependent K+ current (I(K(V))) in GH3 cells. The IC50 value required for the inhibition of I(K(V)) by YC-1 was 1 μM. Unlike YC-1, 8-bromo cGMP did not inhibit I(K(Ca)). However, YC-1 (10 μM) did not affect the amplitude of L-type Ca2+ current. In the cell-attached configuration, application of YC-1 (10 μM) to the bath did not change the single-channel conductance of the large-conductance Ca2+-activated K+ (BK(Ca)) channels; however, it did increase the opening probability of BK(Ca) channels. In contrast, in the outside-out configuration, YC-1 (10 μM) significantly suppressed the opening probability of BK(Ca) channels. The present study shows dual effects of YC-1 on I(K(Ca)) in GH3 cells. The YC-1-mediated stimulation of I(K(Ca)) may result from elevated cytosolic Ca2+, whereas the inhibition of I(K(Ca)) and I(K(V)) by YC-1 appears to be direct and independent of the activation of soluble guanylyl cyclase. Caution thus needs to be used in attributing the YC-1-mediated response to the activation of soluble guanylyl cyclase. Copyright (C) 2000 Elsevier Science Ltd.",
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The mechanism of actions of 3-(5'-(hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) on Ca2+-activated K+ currents in GH3 lactotrophs. / Wu, Sheng-Nan; Hwang, Tsong Long; Teng, Che Ming; Li, Hui Fang; Jan, Chung Ren.

In: Neuropharmacology, Vol. 39, No. 10, 01.09.2000, p. 1788-1799.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The mechanism of actions of 3-(5'-(hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) on Ca2+-activated K+ currents in GH3 lactotrophs

AU - Wu, Sheng-Nan

AU - Hwang, Tsong Long

AU - Teng, Che Ming

AU - Li, Hui Fang

AU - Jan, Chung Ren

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N2 - The effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), an activator of soluble guanylyl cyclase, on ionic currents have been assessed in rat pituitary GH3 lactotrophs. In GH3 cells bathed in normal Tyrode's solution, YC-1 (1 μM) reversibly suppressed the amplitude of the Ca2+-activated K+ current (I(K(Ca))). YC-1 at a concentration above 10 μM produced a biphasic response in the amplitude of I(K(Ca)), i.e., an initial decrease followed by a sustained increase. When the pipette solutions were filled with high EGTA (10 mM), the YC-1-induced stimulatory effect on I(K(Ca)) was abolished. Over a similar concentration range, YC-1 also effectively inhibited the voltage-dependent K+ current (I(K(V))) in GH3 cells. The IC50 value required for the inhibition of I(K(V)) by YC-1 was 1 μM. Unlike YC-1, 8-bromo cGMP did not inhibit I(K(Ca)). However, YC-1 (10 μM) did not affect the amplitude of L-type Ca2+ current. In the cell-attached configuration, application of YC-1 (10 μM) to the bath did not change the single-channel conductance of the large-conductance Ca2+-activated K+ (BK(Ca)) channels; however, it did increase the opening probability of BK(Ca) channels. In contrast, in the outside-out configuration, YC-1 (10 μM) significantly suppressed the opening probability of BK(Ca) channels. The present study shows dual effects of YC-1 on I(K(Ca)) in GH3 cells. The YC-1-mediated stimulation of I(K(Ca)) may result from elevated cytosolic Ca2+, whereas the inhibition of I(K(Ca)) and I(K(V)) by YC-1 appears to be direct and independent of the activation of soluble guanylyl cyclase. Caution thus needs to be used in attributing the YC-1-mediated response to the activation of soluble guanylyl cyclase. Copyright (C) 2000 Elsevier Science Ltd.

AB - The effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), an activator of soluble guanylyl cyclase, on ionic currents have been assessed in rat pituitary GH3 lactotrophs. In GH3 cells bathed in normal Tyrode's solution, YC-1 (1 μM) reversibly suppressed the amplitude of the Ca2+-activated K+ current (I(K(Ca))). YC-1 at a concentration above 10 μM produced a biphasic response in the amplitude of I(K(Ca)), i.e., an initial decrease followed by a sustained increase. When the pipette solutions were filled with high EGTA (10 mM), the YC-1-induced stimulatory effect on I(K(Ca)) was abolished. Over a similar concentration range, YC-1 also effectively inhibited the voltage-dependent K+ current (I(K(V))) in GH3 cells. The IC50 value required for the inhibition of I(K(V)) by YC-1 was 1 μM. Unlike YC-1, 8-bromo cGMP did not inhibit I(K(Ca)). However, YC-1 (10 μM) did not affect the amplitude of L-type Ca2+ current. In the cell-attached configuration, application of YC-1 (10 μM) to the bath did not change the single-channel conductance of the large-conductance Ca2+-activated K+ (BK(Ca)) channels; however, it did increase the opening probability of BK(Ca) channels. In contrast, in the outside-out configuration, YC-1 (10 μM) significantly suppressed the opening probability of BK(Ca) channels. The present study shows dual effects of YC-1 on I(K(Ca)) in GH3 cells. The YC-1-mediated stimulation of I(K(Ca)) may result from elevated cytosolic Ca2+, whereas the inhibition of I(K(Ca)) and I(K(V)) by YC-1 appears to be direct and independent of the activation of soluble guanylyl cyclase. Caution thus needs to be used in attributing the YC-1-mediated response to the activation of soluble guanylyl cyclase. Copyright (C) 2000 Elsevier Science Ltd.

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