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Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, of erg-Mediated Potassium Currents and Intermediate-Conductance Calcium-Activated Potassium Channels
UCL-2077 (triphenylmethylaminomethyl)pyridine) was previously reported to suppress slow afterhyperpolarization in neurons. However, the information with respect to the effects of UCL-2077 on ionic currents is quite scarce. The addition of UCL-2077 decreased the amplitude of erg-mediated K(+) current...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073080/ https://www.ncbi.nlm.nih.gov/pubmed/32093314 http://dx.doi.org/10.3390/ijms21041441 |
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author | Hsu, Hung-Te Lo, Yi-Ching Wu, Sheng-Nan |
author_facet | Hsu, Hung-Te Lo, Yi-Ching Wu, Sheng-Nan |
author_sort | Hsu, Hung-Te |
collection | PubMed |
description | UCL-2077 (triphenylmethylaminomethyl)pyridine) was previously reported to suppress slow afterhyperpolarization in neurons. However, the information with respect to the effects of UCL-2077 on ionic currents is quite scarce. The addition of UCL-2077 decreased the amplitude of erg-mediated K(+) current (I(K(erg))) together with an increased deactivation rate of the current in pituitary GH(3) cells. The IC(50) and K(D) values of UCL-2077-induced inhibition of I(K(erg)) were 4.7 and 5.1 μM, respectively. UCL-2077 (10 μM) distinctly shifted the midpoint in the activation curve of I(K(erg)) to less hyperpolarizing potentials by 17 mV. Its presence decreased the degree of voltage hysteresis for I(K(erg)) elicitation by long-lasting triangular ramp pulse. It also diminished the probability of the opening of intermediate-conductance Ca(2+)-activated K(+) channels. In cell-attached current recordings, UCL-2077 raised the frequency of action currents. When KCNH2 mRNA was knocked down, a UCL-2077-mediated increase in AC firing was attenuated. Collectively, the actions elaborated herein conceivably contribute to the perturbating effects of this compound on electrical behaviors of excitable cells. |
format | Online Article Text |
id | pubmed-7073080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70730802020-03-19 Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, of erg-Mediated Potassium Currents and Intermediate-Conductance Calcium-Activated Potassium Channels Hsu, Hung-Te Lo, Yi-Ching Wu, Sheng-Nan Int J Mol Sci Article UCL-2077 (triphenylmethylaminomethyl)pyridine) was previously reported to suppress slow afterhyperpolarization in neurons. However, the information with respect to the effects of UCL-2077 on ionic currents is quite scarce. The addition of UCL-2077 decreased the amplitude of erg-mediated K(+) current (I(K(erg))) together with an increased deactivation rate of the current in pituitary GH(3) cells. The IC(50) and K(D) values of UCL-2077-induced inhibition of I(K(erg)) were 4.7 and 5.1 μM, respectively. UCL-2077 (10 μM) distinctly shifted the midpoint in the activation curve of I(K(erg)) to less hyperpolarizing potentials by 17 mV. Its presence decreased the degree of voltage hysteresis for I(K(erg)) elicitation by long-lasting triangular ramp pulse. It also diminished the probability of the opening of intermediate-conductance Ca(2+)-activated K(+) channels. In cell-attached current recordings, UCL-2077 raised the frequency of action currents. When KCNH2 mRNA was knocked down, a UCL-2077-mediated increase in AC firing was attenuated. Collectively, the actions elaborated herein conceivably contribute to the perturbating effects of this compound on electrical behaviors of excitable cells. MDPI 2020-02-20 /pmc/articles/PMC7073080/ /pubmed/32093314 http://dx.doi.org/10.3390/ijms21041441 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hsu, Hung-Te Lo, Yi-Ching Wu, Sheng-Nan Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, of erg-Mediated Potassium Currents and Intermediate-Conductance Calcium-Activated Potassium Channels |
title | Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, of erg-Mediated Potassium Currents and Intermediate-Conductance Calcium-Activated Potassium Channels |
title_full | Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, of erg-Mediated Potassium Currents and Intermediate-Conductance Calcium-Activated Potassium Channels |
title_fullStr | Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, of erg-Mediated Potassium Currents and Intermediate-Conductance Calcium-Activated Potassium Channels |
title_full_unstemmed | Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, of erg-Mediated Potassium Currents and Intermediate-Conductance Calcium-Activated Potassium Channels |
title_short | Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, of erg-Mediated Potassium Currents and Intermediate-Conductance Calcium-Activated Potassium Channels |
title_sort | characterization of convergent suppression by ucl-2077 (3-(triphenylmethylaminomethyl)pyridine), known to inhibit slow afterhyperpolarization, of erg-mediated potassium currents and intermediate-conductance calcium-activated potassium channels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073080/ https://www.ncbi.nlm.nih.gov/pubmed/32093314 http://dx.doi.org/10.3390/ijms21041441 |
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