Antiarrhythmic effect of either negative modulation or blockade of small conductance Ca2+ activated K+ channels on ventricular fibrillation in guinea pig Langendorff perfused heart

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Antiarrhythmic effect of either negative modulation or blockade of small conductance Ca2+ activated K+ channels on ventricular fibrillation in guinea pig Langendorff perfused heart. / Diness, Jonas Goldin; Kirchhoff, Jeppe Egedal; Sheykhzade, Majid; Jespersen, Thomas; Grunnet, Morten.

In: Journal of Cardiovascular Pharmacology, Vol. 66, No. 3, 08.05.2015, p. 294–299.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Diness, JG, Kirchhoff, JE, Sheykhzade, M, Jespersen, T & Grunnet, M 2015, 'Antiarrhythmic effect of either negative modulation or blockade of small conductance Ca2+ activated K+ channels on ventricular fibrillation in guinea pig Langendorff perfused heart', Journal of Cardiovascular Pharmacology, vol. 66, no. 3, pp. 294–299. https://doi.org/10.1097/FJC.0000000000000278

APA

Diness, J. G., Kirchhoff, J. E., Sheykhzade, M., Jespersen, T., & Grunnet, M. (2015). Antiarrhythmic effect of either negative modulation or blockade of small conductance Ca2+ activated K+ channels on ventricular fibrillation in guinea pig Langendorff perfused heart. Journal of Cardiovascular Pharmacology, 66(3), 294–299. https://doi.org/10.1097/FJC.0000000000000278

Vancouver

Diness JG, Kirchhoff JE, Sheykhzade M, Jespersen T, Grunnet M. Antiarrhythmic effect of either negative modulation or blockade of small conductance Ca2+ activated K+ channels on ventricular fibrillation in guinea pig Langendorff perfused heart. Journal of Cardiovascular Pharmacology. 2015 May 8;66(3):294–299. https://doi.org/10.1097/FJC.0000000000000278

Author

Diness, Jonas Goldin ; Kirchhoff, Jeppe Egedal ; Sheykhzade, Majid ; Jespersen, Thomas ; Grunnet, Morten. / Antiarrhythmic effect of either negative modulation or blockade of small conductance Ca2+ activated K+ channels on ventricular fibrillation in guinea pig Langendorff perfused heart. In: Journal of Cardiovascular Pharmacology. 2015 ; Vol. 66, No. 3. pp. 294–299.

Bibtex

@article{a7d007cf3a424d4cb5bb15ed73b29d19,
title = "Antiarrhythmic effect of either negative modulation or blockade of small conductance Ca2+ activated K+ channels on ventricular fibrillation in guinea pig Langendorff perfused heart",
abstract = "During recent years small conductance Ca activated K (SK) channels have been reported to play a role in cardiac electrophysiology. SK channels seem to be expressed in atria and ventricles but from a functional perspective atrial activity is predominant. A general notion seems to be that cardiac SK channels are predominantly coming into play during arrhythmogenic events where intracellular concentration of Ca is increased. During ventricular fibrillation a surge of [Ca]i has the potential to bind to and open SK channels. To obtain mechanistic insight into possible roles of SK channels during ventricular fibrillation we conducted experiments with a SK channel pore blocker (ICA) and a negatively allosteric modulator (NS8395) in a Langendorff perfused heart model. Both compounds increased the action potential duration (APD), effective refractory period (ERP) and Wenckebach cycle length (WCL) to comparable extents. Despite these similarities, the SK channel modulator was found to revert and prevent ventricular fibrillation (VF) more efficiently than the SK channel pore blocker. In conclusion, either negative allosteric modulation of the SK channel with NS8593 is more favorable than pure channel block with ICA or the two compounds have different selectivity profiles which makes NS8593 more antiarrhythmic than ICA in a setting of VF.",
author = "Diness, {Jonas Goldin} and Kirchhoff, {Jeppe Egedal} and Majid Sheykhzade and Thomas Jespersen and Morten Grunnet",
year = "2015",
month = "5",
day = "8",
doi = "10.1097/FJC.0000000000000278",
language = "English",
volume = "66",
pages = "294–299",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams & Wilkins",
number = "3",

}

RIS

TY - JOUR

T1 - Antiarrhythmic effect of either negative modulation or blockade of small conductance Ca2+ activated K+ channels on ventricular fibrillation in guinea pig Langendorff perfused heart

AU - Diness, Jonas Goldin

AU - Kirchhoff, Jeppe Egedal

AU - Sheykhzade, Majid

AU - Jespersen, Thomas

AU - Grunnet, Morten

PY - 2015/5/8

Y1 - 2015/5/8

N2 - During recent years small conductance Ca activated K (SK) channels have been reported to play a role in cardiac electrophysiology. SK channels seem to be expressed in atria and ventricles but from a functional perspective atrial activity is predominant. A general notion seems to be that cardiac SK channels are predominantly coming into play during arrhythmogenic events where intracellular concentration of Ca is increased. During ventricular fibrillation a surge of [Ca]i has the potential to bind to and open SK channels. To obtain mechanistic insight into possible roles of SK channels during ventricular fibrillation we conducted experiments with a SK channel pore blocker (ICA) and a negatively allosteric modulator (NS8395) in a Langendorff perfused heart model. Both compounds increased the action potential duration (APD), effective refractory period (ERP) and Wenckebach cycle length (WCL) to comparable extents. Despite these similarities, the SK channel modulator was found to revert and prevent ventricular fibrillation (VF) more efficiently than the SK channel pore blocker. In conclusion, either negative allosteric modulation of the SK channel with NS8593 is more favorable than pure channel block with ICA or the two compounds have different selectivity profiles which makes NS8593 more antiarrhythmic than ICA in a setting of VF.

AB - During recent years small conductance Ca activated K (SK) channels have been reported to play a role in cardiac electrophysiology. SK channels seem to be expressed in atria and ventricles but from a functional perspective atrial activity is predominant. A general notion seems to be that cardiac SK channels are predominantly coming into play during arrhythmogenic events where intracellular concentration of Ca is increased. During ventricular fibrillation a surge of [Ca]i has the potential to bind to and open SK channels. To obtain mechanistic insight into possible roles of SK channels during ventricular fibrillation we conducted experiments with a SK channel pore blocker (ICA) and a negatively allosteric modulator (NS8395) in a Langendorff perfused heart model. Both compounds increased the action potential duration (APD), effective refractory period (ERP) and Wenckebach cycle length (WCL) to comparable extents. Despite these similarities, the SK channel modulator was found to revert and prevent ventricular fibrillation (VF) more efficiently than the SK channel pore blocker. In conclusion, either negative allosteric modulation of the SK channel with NS8593 is more favorable than pure channel block with ICA or the two compounds have different selectivity profiles which makes NS8593 more antiarrhythmic than ICA in a setting of VF.

UR - https://www.ncbi.nlm.nih.gov/pubmed/25978690

U2 - 10.1097/FJC.0000000000000278

DO - 10.1097/FJC.0000000000000278

M3 - Journal article

C2 - 25978690

VL - 66

SP - 294

EP - 299

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 3

ER -

ID: 137555844