Research ExplorerPublicationsOverexpression of KCNN3 results in sudden cardiac death

Overexpression of KCNN3 results in sudden cardiac death

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Overexpression of KCNN3 results in sudden cardiac death. / Mahida, Saagar; Mills, Robert W; Tucker, Nathan R; Simonson, Bridget; Macri, Vincenzo; Lemoine, Marc D; Das, Saumya; Milan, David J; Ellinor, Patrick T.

In: CARDIOVASC RES, Vol. 101, No. 2, 01.02.2014, p. 326-334.

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

Harvard

Mahida, S, Mills, RW, Tucker, NR, Simonson, B, Macri, V, Lemoine, MD, Das, S, Milan, DJ & Ellinor, PT 2014, 'Overexpression of KCNN3 results in sudden cardiac death', CARDIOVASC RES, vol. 101, no. 2, pp. 326-334. https://doi.org/10.1093/cvr/cvt269

APA

Mahida, S., Mills, R. W., Tucker, N. R., Simonson, B., Macri, V., Lemoine, M. D., Das, S., Milan, D. J., & Ellinor, P. T. (2014). Overexpression of KCNN3 results in sudden cardiac death. CARDIOVASC RES, 101(2), 326-334. https://doi.org/10.1093/cvr/cvt269

Vancouver

Mahida S, Mills RW, Tucker NR, Simonson B, Macri V, Lemoine MD et al. Overexpression of KCNN3 results in sudden cardiac death. CARDIOVASC RES. 2014 Feb 1;101(2):326-334. https://doi.org/10.1093/cvr/cvt269

Bibtex

@article{6d0d3dfac2b64c469aed4d1f5906e7e5,
title = "Overexpression of KCNN3 results in sudden cardiac death",
abstract = "BACKGROUND: A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias.METHODS AND RESULTS: We characterized the cardiac electrophysiological phenotype of a mouse line with overexpression of the SK3 channel. We generated homozygote (SK3(T/T)) and heterozygote (SK3(+/T)) mice with overexpression of the channel and compared them with wild-type (WT) controls. We observed a high incidence of sudden death among SK3(T/T) mice (7 of 19 SK3(T/T) mice). Ambulatory monitoring demonstrated that sudden death was due to heart block and bradyarrhythmias. SK3(T/T) mice displayed normal body weight, temperature, and cardiac function on echocardiography; however, histological analysis demonstrated that these mice have abnormal atrioventricular node morphology. Optical mapping demonstrated that SK3(T/T) mice have slower ventricular conduction compared with WT controls (SK3(T/T) vs. WT; 0.45 ± 0.04 vs. 0.60 ± 0.09 mm/ms, P = 0.001). Programmed stimulation in 1-month-old SK3(T/T) mice demonstrated inducible atrial arrhythmias (50% of SK3(T/T) vs. 0% of WT mice) and also a shorter atrioventricular nodal refractory period (SK3(T/T) vs. WT; 43 ± 6 vs. 52 ± 9 ms, P = 0.02). Three-month-old SK3(T/T) mice on the other hand displayed a trend towards a more prolonged atrioventricular nodal refractory period (SK3(T/T) vs. WT; 61 ± 1 vs. 52 ± 6 ms, P = 0.06).CONCLUSION: Overexpression of the SK3 channel causes an increased risk of sudden death associated with bradyarrhythmias and heart block, possibly due to atrioventricular nodal dysfunction.",
keywords = "Action Potentials, Animals, Atrioventricular Node/abnormalities, Bradycardia/genetics, Cardiac Pacing, Artificial, Connexin 43/metabolism, Death, Sudden, Cardiac/etiology, Electrocardiography, Ambulatory, Genetic Predisposition to Disease, Heart Block/genetics, Heterozygote, Homozygote, Mice, Mice, Transgenic, Phenotype, Small-Conductance Calcium-Activated Potassium Channels/genetics, Time Factors, Up-Regulation, Voltage-Sensitive Dye Imaging",
author = "Saagar Mahida and Mills, {Robert W} and Tucker, {Nathan R} and Bridget Simonson and Vincenzo Macri and Lemoine, {Marc D} and Saumya Das and Milan, {David J} and Ellinor, {Patrick T}",
year = "2014",
month = feb,
day = "1",
doi = "10.1093/cvr/cvt269",
language = "English",
volume = "101",
pages = "326--334",
journal = "CARDIOVASC RES",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - Overexpression of KCNN3 results in sudden cardiac death

AU - Mahida, Saagar

AU - Mills, Robert W

AU - Tucker, Nathan R

AU - Simonson, Bridget

AU - Macri, Vincenzo

AU - Lemoine, Marc D

AU - Das, Saumya

AU - Milan, David J

AU - Ellinor, Patrick T

PY - 2014/2/1

Y1 - 2014/2/1

N2 - BACKGROUND: A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias.METHODS AND RESULTS: We characterized the cardiac electrophysiological phenotype of a mouse line with overexpression of the SK3 channel. We generated homozygote (SK3(T/T)) and heterozygote (SK3(+/T)) mice with overexpression of the channel and compared them with wild-type (WT) controls. We observed a high incidence of sudden death among SK3(T/T) mice (7 of 19 SK3(T/T) mice). Ambulatory monitoring demonstrated that sudden death was due to heart block and bradyarrhythmias. SK3(T/T) mice displayed normal body weight, temperature, and cardiac function on echocardiography; however, histological analysis demonstrated that these mice have abnormal atrioventricular node morphology. Optical mapping demonstrated that SK3(T/T) mice have slower ventricular conduction compared with WT controls (SK3(T/T) vs. WT; 0.45 ± 0.04 vs. 0.60 ± 0.09 mm/ms, P = 0.001). Programmed stimulation in 1-month-old SK3(T/T) mice demonstrated inducible atrial arrhythmias (50% of SK3(T/T) vs. 0% of WT mice) and also a shorter atrioventricular nodal refractory period (SK3(T/T) vs. WT; 43 ± 6 vs. 52 ± 9 ms, P = 0.02). Three-month-old SK3(T/T) mice on the other hand displayed a trend towards a more prolonged atrioventricular nodal refractory period (SK3(T/T) vs. WT; 61 ± 1 vs. 52 ± 6 ms, P = 0.06).CONCLUSION: Overexpression of the SK3 channel causes an increased risk of sudden death associated with bradyarrhythmias and heart block, possibly due to atrioventricular nodal dysfunction.

AB - BACKGROUND: A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias.METHODS AND RESULTS: We characterized the cardiac electrophysiological phenotype of a mouse line with overexpression of the SK3 channel. We generated homozygote (SK3(T/T)) and heterozygote (SK3(+/T)) mice with overexpression of the channel and compared them with wild-type (WT) controls. We observed a high incidence of sudden death among SK3(T/T) mice (7 of 19 SK3(T/T) mice). Ambulatory monitoring demonstrated that sudden death was due to heart block and bradyarrhythmias. SK3(T/T) mice displayed normal body weight, temperature, and cardiac function on echocardiography; however, histological analysis demonstrated that these mice have abnormal atrioventricular node morphology. Optical mapping demonstrated that SK3(T/T) mice have slower ventricular conduction compared with WT controls (SK3(T/T) vs. WT; 0.45 ± 0.04 vs. 0.60 ± 0.09 mm/ms, P = 0.001). Programmed stimulation in 1-month-old SK3(T/T) mice demonstrated inducible atrial arrhythmias (50% of SK3(T/T) vs. 0% of WT mice) and also a shorter atrioventricular nodal refractory period (SK3(T/T) vs. WT; 43 ± 6 vs. 52 ± 9 ms, P = 0.02). Three-month-old SK3(T/T) mice on the other hand displayed a trend towards a more prolonged atrioventricular nodal refractory period (SK3(T/T) vs. WT; 61 ± 1 vs. 52 ± 6 ms, P = 0.06).CONCLUSION: Overexpression of the SK3 channel causes an increased risk of sudden death associated with bradyarrhythmias and heart block, possibly due to atrioventricular nodal dysfunction.

KW - Action Potentials

KW - Animals

KW - Atrioventricular Node/abnormalities

KW - Bradycardia/genetics

KW - Cardiac Pacing, Artificial

KW - Connexin 43/metabolism

KW - Death, Sudden, Cardiac/etiology

KW - Electrocardiography, Ambulatory

KW - Genetic Predisposition to Disease

KW - Heart Block/genetics

KW - Heterozygote

KW - Homozygote

KW - Mice

KW - Mice, Transgenic

KW - Phenotype

KW - Small-Conductance Calcium-Activated Potassium Channels/genetics

KW - Time Factors

KW - Up-Regulation

KW - Voltage-Sensitive Dye Imaging

U2 - 10.1093/cvr/cvt269

DO - 10.1093/cvr/cvt269

M3 - SCORING: Journal article

C2 - 24296650

VL - 101

SP - 326

EP - 334

JO - CARDIOVASC RES

JF - CARDIOVASC RES

SN - 0008-6363

IS - 2

ER -