Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo

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Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo. / Bentzen, Bo Hjorth; Andersen, Rune Wederkinck; Olesen, Søren-Peter; Grunnet, Morten; Nardi, Antonio.

In: NAUNYN-SCHMIEDEBERGS ARCHIV FUR EXPERIMENTELLE PATHOLOGIE UND PHARMAKOLOGIE, 2009.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Bentzen, BH, Andersen, RW, Olesen, S-P, Grunnet, M & Nardi, A 2009, 'Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo', NAUNYN-SCHMIEDEBERGS ARCHIV FUR EXPERIMENTELLE PATHOLOGIE UND PHARMAKOLOGIE. https://doi.org/10.1007/s00210-009-0456-2

APA

Bentzen, B. H., Andersen, R. W., Olesen, S-P., Grunnet, M., & Nardi, A. (2009). Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo. NAUNYN-SCHMIEDEBERGS ARCHIV FUR EXPERIMENTELLE PATHOLOGIE UND PHARMAKOLOGIE. https://doi.org/10.1007/s00210-009-0456-2

Vancouver

Bentzen BH, Andersen RW, Olesen S-P, Grunnet M, Nardi A. Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo. NAUNYN-SCHMIEDEBERGS ARCHIV FUR EXPERIMENTELLE PATHOLOGIE UND PHARMAKOLOGIE. 2009. https://doi.org/10.1007/s00210-009-0456-2

Author

Bentzen, Bo Hjorth ; Andersen, Rune Wederkinck ; Olesen, Søren-Peter ; Grunnet, Morten ; Nardi, Antonio. / Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo. In: NAUNYN-SCHMIEDEBERGS ARCHIV FUR EXPERIMENTELLE PATHOLOGIE UND PHARMAKOLOGIE. 2009.

Bibtex

@article{b09c5680334511df8ed1000ea68e967b,
title = "Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo",
abstract = "Pharmacological activation of the large-conductance Ca(2+)-activated K(+) channel (KCa1.1) in the cardiac inner mitochondrial membrane has been found to protect the heart against ischemia reperfusion injuries. However, there are concerns about the selectivity of the pharmacological tools used to modulate the channel. Here, we address this issue by synthesising a methylated analogue of the tool KCa1.1 channel activator NS11021. The compound (NS13558) is designed as a structurally closely related and biologically inactive analogue of NS11021. NS13558 did not elicit any significant opening of cloned human KCa1.1 channels, but maintained comparable biological activity towards other cardiac ion channels as compared to NS11021. In isolated perfused rat hearts subjected to ischemia-reperfusion, infarct size was reduced from 29% in control to 7% in NS11021 treated hearts. In comparison, the inactive derivate of NS11021, i.e., NS13558, did not confer any cardioprotection, demonstrated by an infarct size identical to control hearts. This suggests that NS11021 exerts its primary effect through KCa1.1 channels, which indicates an important role of these channels in protection against ischemia-reperfusion injuries. Furthermore, the study demonstrates a novel way of combining an activator of the KCa1.1 channel (NS11021) and its structurally closely related inactive analogue NS13558 to address the functional role of KCa1.1 channels, and we believe these novel tools may constitute a valuable addition to understanding the functional role of KCa1.1 channels under physiological and pathophysiological conditions.",
author = "Bentzen, {Bo Hjorth} and Andersen, {Rune Wederkinck} and S{\o}ren-Peter Olesen and Morten Grunnet and Antonio Nardi",
year = "2009",
doi = "10.1007/s00210-009-0456-2",
language = "English",
journal = "NAUNYN-SCHMIEDEBERGS ARCHIV FUR EXPERIMENTELLE PATHOLOGIE UND PHARMAKOLOGIE",
issn = "0365-2009",

}

RIS

TY - JOUR

T1 - Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo

AU - Bentzen, Bo Hjorth

AU - Andersen, Rune Wederkinck

AU - Olesen, Søren-Peter

AU - Grunnet, Morten

AU - Nardi, Antonio

PY - 2009

Y1 - 2009

N2 - Pharmacological activation of the large-conductance Ca(2+)-activated K(+) channel (KCa1.1) in the cardiac inner mitochondrial membrane has been found to protect the heart against ischemia reperfusion injuries. However, there are concerns about the selectivity of the pharmacological tools used to modulate the channel. Here, we address this issue by synthesising a methylated analogue of the tool KCa1.1 channel activator NS11021. The compound (NS13558) is designed as a structurally closely related and biologically inactive analogue of NS11021. NS13558 did not elicit any significant opening of cloned human KCa1.1 channels, but maintained comparable biological activity towards other cardiac ion channels as compared to NS11021. In isolated perfused rat hearts subjected to ischemia-reperfusion, infarct size was reduced from 29% in control to 7% in NS11021 treated hearts. In comparison, the inactive derivate of NS11021, i.e., NS13558, did not confer any cardioprotection, demonstrated by an infarct size identical to control hearts. This suggests that NS11021 exerts its primary effect through KCa1.1 channels, which indicates an important role of these channels in protection against ischemia-reperfusion injuries. Furthermore, the study demonstrates a novel way of combining an activator of the KCa1.1 channel (NS11021) and its structurally closely related inactive analogue NS13558 to address the functional role of KCa1.1 channels, and we believe these novel tools may constitute a valuable addition to understanding the functional role of KCa1.1 channels under physiological and pathophysiological conditions.

AB - Pharmacological activation of the large-conductance Ca(2+)-activated K(+) channel (KCa1.1) in the cardiac inner mitochondrial membrane has been found to protect the heart against ischemia reperfusion injuries. However, there are concerns about the selectivity of the pharmacological tools used to modulate the channel. Here, we address this issue by synthesising a methylated analogue of the tool KCa1.1 channel activator NS11021. The compound (NS13558) is designed as a structurally closely related and biologically inactive analogue of NS11021. NS13558 did not elicit any significant opening of cloned human KCa1.1 channels, but maintained comparable biological activity towards other cardiac ion channels as compared to NS11021. In isolated perfused rat hearts subjected to ischemia-reperfusion, infarct size was reduced from 29% in control to 7% in NS11021 treated hearts. In comparison, the inactive derivate of NS11021, i.e., NS13558, did not confer any cardioprotection, demonstrated by an infarct size identical to control hearts. This suggests that NS11021 exerts its primary effect through KCa1.1 channels, which indicates an important role of these channels in protection against ischemia-reperfusion injuries. Furthermore, the study demonstrates a novel way of combining an activator of the KCa1.1 channel (NS11021) and its structurally closely related inactive analogue NS13558 to address the functional role of KCa1.1 channels, and we believe these novel tools may constitute a valuable addition to understanding the functional role of KCa1.1 channels under physiological and pathophysiological conditions.

U2 - 10.1007/s00210-009-0456-2

DO - 10.1007/s00210-009-0456-2

M3 - Journal article

C2 - 19798481

JO - NAUNYN-SCHMIEDEBERGS ARCHIV FUR EXPERIMENTELLE PATHOLOGIE UND PHARMAKOLOGIE

JF - NAUNYN-SCHMIEDEBERGS ARCHIV FUR EXPERIMENTELLE PATHOLOGIE UND PHARMAKOLOGIE

SN - 0365-2009

ER -

ID: 18699875