Small conductance calcium activated K+ channel inhibitor decreases stretch induced vulnerability to atrial fibrillation

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Small conductance calcium activated K+ channel inhibitor decreases stretch induced vulnerability to atrial fibrillation. / Yan, Yannan; Skarsfeldt, Mark Alexander; Diness, Jonas Goldin; Bentzen, Bo Hjorth.

In: IJC Heart and Vasculature, Vol. 37, 100898, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Yan, Y, Skarsfeldt, MA, Diness, JG & Bentzen, BH 2021, 'Small conductance calcium activated K+ channel inhibitor decreases stretch induced vulnerability to atrial fibrillation', IJC Heart and Vasculature, vol. 37, 100898. https://doi.org/10.1016/j.ijcha.2021.100898

APA

Yan, Y., Skarsfeldt, M. A., Diness, J. G., & Bentzen, B. H. (2021). Small conductance calcium activated K+ channel inhibitor decreases stretch induced vulnerability to atrial fibrillation. IJC Heart and Vasculature, 37, [100898]. https://doi.org/10.1016/j.ijcha.2021.100898

Vancouver

Yan Y, Skarsfeldt MA, Diness JG, Bentzen BH. Small conductance calcium activated K+ channel inhibitor decreases stretch induced vulnerability to atrial fibrillation. IJC Heart and Vasculature. 2021;37. 100898. https://doi.org/10.1016/j.ijcha.2021.100898

Author

Yan, Yannan ; Skarsfeldt, Mark Alexander ; Diness, Jonas Goldin ; Bentzen, Bo Hjorth. / Small conductance calcium activated K+ channel inhibitor decreases stretch induced vulnerability to atrial fibrillation. In: IJC Heart and Vasculature. 2021 ; Vol. 37.

Bibtex

@article{e8fa1d84e3e5450ebc9ab678e3f0e41d,
title = "Small conductance calcium activated K+ channel inhibitor decreases stretch induced vulnerability to atrial fibrillation",
abstract = "Background: Atrial dilation is an important risk factor for atrial fibrillation (AF) and animal studies have found that acute atrial dilation shortens the atrial effective refractory period (AERP) and increases the risk of AF. Stretch activated ion channels (SACs) and calcium channels play a role in this. The expression profile and calcium dependent activation makes the small conductance calcium activated K+ channel (K(Ca)2.x) a candidate for coupling stretch induced increases in intracellular calcium through K+-efflux and thereby shortening of atrial refractoriness.Objectives: We hypothesized that K(Ca)2.x channel inhibitors can prevent the stretch induced shortening of AERP and protect the heart from AF.Methods: The effect of K(Ca)2 channel inhibitor (N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) 1 mu M) was investigated using the isolated perfused rabbit heart preparation. To stretch the left atrium (LA) a balloon was inserted and inflated. AERP and action potential duration (APD) were recorded before and after atrial stretch. AF was induced by burst pacing the LA at different degrees of atrial stretch.Results: Stretching of the LA by increasing the balloon pressure from 0 to 20 mmHg shortened the AERP by 8.6 +/- 1 ms. In comparison, the K(Ca)2 inhibitor ICA significantly attenuated the stretch induced shortening of AERP to 2.5 +/- 1.1 ms. Total AF duration increased linearly with atrial balloon pressure. This relationship was not found in the presence of ICA. ICA lowered the incidence of AF induction and total AF duration.Conclusion: The K(Ca)2 channel inhibitor ICA attenuates the acute stretch induced shortening of AERP and decreases stretch induced vulnerability to AF.",
keywords = "Ion channel, Atrial fibrillation, SK channel, K(Ca)2, Stretch, Pharmacology, REFRACTORY PERIOD, INDUCIBILITY, DILATATION, GADOLINIUM, PRESSURE, FEEDBACK, SK2",
author = "Yannan Yan and Skarsfeldt, {Mark Alexander} and Diness, {Jonas Goldin} and Bentzen, {Bo Hjorth}",
year = "2021",
doi = "10.1016/j.ijcha.2021.100898",
language = "English",
volume = "37",
journal = "IJC Heart and Vasculature",
issn = "2352-9067",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Small conductance calcium activated K+ channel inhibitor decreases stretch induced vulnerability to atrial fibrillation

AU - Yan, Yannan

AU - Skarsfeldt, Mark Alexander

AU - Diness, Jonas Goldin

AU - Bentzen, Bo Hjorth

PY - 2021

Y1 - 2021

N2 - Background: Atrial dilation is an important risk factor for atrial fibrillation (AF) and animal studies have found that acute atrial dilation shortens the atrial effective refractory period (AERP) and increases the risk of AF. Stretch activated ion channels (SACs) and calcium channels play a role in this. The expression profile and calcium dependent activation makes the small conductance calcium activated K+ channel (K(Ca)2.x) a candidate for coupling stretch induced increases in intracellular calcium through K+-efflux and thereby shortening of atrial refractoriness.Objectives: We hypothesized that K(Ca)2.x channel inhibitors can prevent the stretch induced shortening of AERP and protect the heart from AF.Methods: The effect of K(Ca)2 channel inhibitor (N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) 1 mu M) was investigated using the isolated perfused rabbit heart preparation. To stretch the left atrium (LA) a balloon was inserted and inflated. AERP and action potential duration (APD) were recorded before and after atrial stretch. AF was induced by burst pacing the LA at different degrees of atrial stretch.Results: Stretching of the LA by increasing the balloon pressure from 0 to 20 mmHg shortened the AERP by 8.6 +/- 1 ms. In comparison, the K(Ca)2 inhibitor ICA significantly attenuated the stretch induced shortening of AERP to 2.5 +/- 1.1 ms. Total AF duration increased linearly with atrial balloon pressure. This relationship was not found in the presence of ICA. ICA lowered the incidence of AF induction and total AF duration.Conclusion: The K(Ca)2 channel inhibitor ICA attenuates the acute stretch induced shortening of AERP and decreases stretch induced vulnerability to AF.

AB - Background: Atrial dilation is an important risk factor for atrial fibrillation (AF) and animal studies have found that acute atrial dilation shortens the atrial effective refractory period (AERP) and increases the risk of AF. Stretch activated ion channels (SACs) and calcium channels play a role in this. The expression profile and calcium dependent activation makes the small conductance calcium activated K+ channel (K(Ca)2.x) a candidate for coupling stretch induced increases in intracellular calcium through K+-efflux and thereby shortening of atrial refractoriness.Objectives: We hypothesized that K(Ca)2.x channel inhibitors can prevent the stretch induced shortening of AERP and protect the heart from AF.Methods: The effect of K(Ca)2 channel inhibitor (N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) 1 mu M) was investigated using the isolated perfused rabbit heart preparation. To stretch the left atrium (LA) a balloon was inserted and inflated. AERP and action potential duration (APD) were recorded before and after atrial stretch. AF was induced by burst pacing the LA at different degrees of atrial stretch.Results: Stretching of the LA by increasing the balloon pressure from 0 to 20 mmHg shortened the AERP by 8.6 +/- 1 ms. In comparison, the K(Ca)2 inhibitor ICA significantly attenuated the stretch induced shortening of AERP to 2.5 +/- 1.1 ms. Total AF duration increased linearly with atrial balloon pressure. This relationship was not found in the presence of ICA. ICA lowered the incidence of AF induction and total AF duration.Conclusion: The K(Ca)2 channel inhibitor ICA attenuates the acute stretch induced shortening of AERP and decreases stretch induced vulnerability to AF.

KW - Ion channel

KW - Atrial fibrillation

KW - SK channel

KW - K(Ca)2

KW - Stretch

KW - Pharmacology

KW - REFRACTORY PERIOD

KW - INDUCIBILITY

KW - DILATATION

KW - GADOLINIUM

KW - PRESSURE

KW - FEEDBACK

KW - SK2

U2 - 10.1016/j.ijcha.2021.100898

DO - 10.1016/j.ijcha.2021.100898

M3 - Journal article

C2 - 34746364

VL - 37

JO - IJC Heart and Vasculature

JF - IJC Heart and Vasculature

SN - 2352-9067

M1 - 100898

ER -

ID: 286414803