Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2

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Standard

Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2. / Grubb, Søren Jahn; Aistrup, Gary L; Koivumäki, Jussi T; Speerschneider, Tobias; Gottlieb, Lisa Amalie; Mutsaers, Nancy A. M.; Olesen, Søren-Peter; Callø, Kirstine; Thomsen, Morten Bækgaard.

I: American Journal of Physiology: Heart and Circulatory Physiology, Bind 309, Nr. 3, 01.08.2015, s. H481-H489.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Grubb, SJ, Aistrup, GL, Koivumäki, JT, Speerschneider, T, Gottlieb, LA, Mutsaers, NAM, Olesen, S-P, Callø, K & Thomsen, MB 2015, 'Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2', American Journal of Physiology: Heart and Circulatory Physiology, bind 309, nr. 3, s. H481-H489. https://doi.org/10.1152/ajpheart.00166.2015

APA

Grubb, S. J., Aistrup, G. L., Koivumäki, J. T., Speerschneider, T., Gottlieb, L. A., Mutsaers, N. A. M., ... Thomsen, M. B. (2015). Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2. American Journal of Physiology: Heart and Circulatory Physiology, 309(3), H481-H489. https://doi.org/10.1152/ajpheart.00166.2015

Vancouver

Grubb SJ, Aistrup GL, Koivumäki JT, Speerschneider T, Gottlieb LA, Mutsaers NAM o.a. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2. American Journal of Physiology: Heart and Circulatory Physiology. 2015 aug 1;309(3):H481-H489. https://doi.org/10.1152/ajpheart.00166.2015

Author

Grubb, Søren Jahn ; Aistrup, Gary L ; Koivumäki, Jussi T ; Speerschneider, Tobias ; Gottlieb, Lisa Amalie ; Mutsaers, Nancy A. M. ; Olesen, Søren-Peter ; Callø, Kirstine ; Thomsen, Morten Bækgaard. / Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2. I: American Journal of Physiology: Heart and Circulatory Physiology. 2015 ; Bind 309, Nr. 3. s. H481-H489.

Bibtex

@article{9a5d4b832c3240b596687ab16c4f4a7e,
title = "Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2",
abstract = "Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with both Kv4 to conduct the fast-recovering transient outward K(+) current (Ito,f) and with CaV1.2 to mediate the inward L-type Ca(2+) current (ICa,L). Anesthetized KChIP2(-/-) mice have normal cardiac contraction despite the lower ICa,L, and we hypothesized that the delayed repolarization could contribute to the preservation of contractile function. Detailed analysis of current kinetics shows that only ICa,L density is reduced, and immunoblots demonstrate unaltered CaV1.2 and CaVβ2 protein levels. Computer modeling suggests that delayed repolarization would prolong the period of Ca(2+) entry into the cell, thereby augmenting Ca(2+)-induced Ca(2+) release. Ca(2+) transients in disaggregated KChIP2(-/-) cardiomyocytes are indeed comparable to wild-type transients, corroborating the preserved contractile function and suggesting that the compensatory mechanism lies in the Ca(2+)-induced Ca(2+) release event. We next functionally probed dyad structure, ryanodine receptor Ca(2+) sensitivity, and sarcoplasmic reticulum Ca(2+) load and found that increased temporal synchronicity of the Ca(2+) release in KChIP2(-/-) cardiomyocytes may reflect improved dyad structure aiding the compensatory mechanisms in preserving cardiac contractile force. Thus the bimodal effect of KChIP2 on Ito,f and ICa,L constitutes an important regulatory effect of KChIP2 on cardiac contractility, and we conclude that delayed repolarization and improved dyad structure function together to preserve cardiac contraction in KChIP2(-/-) mice.",
author = "Grubb, {S{\o}ren Jahn} and Aistrup, {Gary L} and Koivum{\"a}ki, {Jussi T} and Tobias Speerschneider and Gottlieb, {Lisa Amalie} and Mutsaers, {Nancy A. M.} and S{\o}ren-Peter Olesen and Kirstine Call{\o} and Thomsen, {Morten B{\ae}kgaard}",
note = "Copyright {\circledC} 2015 the American Physiological Society.",
year = "2015",
month = "8",
day = "1",
doi = "10.1152/ajpheart.00166.2015",
language = "English",
volume = "309",
pages = "H481--H489",
journal = "American Journal of Physiology: Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "3",

}

RIS

TY - JOUR

T1 - Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2

AU - Grubb, Søren Jahn

AU - Aistrup, Gary L

AU - Koivumäki, Jussi T

AU - Speerschneider, Tobias

AU - Gottlieb, Lisa Amalie

AU - Mutsaers, Nancy A. M.

AU - Olesen, Søren-Peter

AU - Callø, Kirstine

AU - Thomsen, Morten Bækgaard

N1 - Copyright © 2015 the American Physiological Society.

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with both Kv4 to conduct the fast-recovering transient outward K(+) current (Ito,f) and with CaV1.2 to mediate the inward L-type Ca(2+) current (ICa,L). Anesthetized KChIP2(-/-) mice have normal cardiac contraction despite the lower ICa,L, and we hypothesized that the delayed repolarization could contribute to the preservation of contractile function. Detailed analysis of current kinetics shows that only ICa,L density is reduced, and immunoblots demonstrate unaltered CaV1.2 and CaVβ2 protein levels. Computer modeling suggests that delayed repolarization would prolong the period of Ca(2+) entry into the cell, thereby augmenting Ca(2+)-induced Ca(2+) release. Ca(2+) transients in disaggregated KChIP2(-/-) cardiomyocytes are indeed comparable to wild-type transients, corroborating the preserved contractile function and suggesting that the compensatory mechanism lies in the Ca(2+)-induced Ca(2+) release event. We next functionally probed dyad structure, ryanodine receptor Ca(2+) sensitivity, and sarcoplasmic reticulum Ca(2+) load and found that increased temporal synchronicity of the Ca(2+) release in KChIP2(-/-) cardiomyocytes may reflect improved dyad structure aiding the compensatory mechanisms in preserving cardiac contractile force. Thus the bimodal effect of KChIP2 on Ito,f and ICa,L constitutes an important regulatory effect of KChIP2 on cardiac contractility, and we conclude that delayed repolarization and improved dyad structure function together to preserve cardiac contraction in KChIP2(-/-) mice.

AB - Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with both Kv4 to conduct the fast-recovering transient outward K(+) current (Ito,f) and with CaV1.2 to mediate the inward L-type Ca(2+) current (ICa,L). Anesthetized KChIP2(-/-) mice have normal cardiac contraction despite the lower ICa,L, and we hypothesized that the delayed repolarization could contribute to the preservation of contractile function. Detailed analysis of current kinetics shows that only ICa,L density is reduced, and immunoblots demonstrate unaltered CaV1.2 and CaVβ2 protein levels. Computer modeling suggests that delayed repolarization would prolong the period of Ca(2+) entry into the cell, thereby augmenting Ca(2+)-induced Ca(2+) release. Ca(2+) transients in disaggregated KChIP2(-/-) cardiomyocytes are indeed comparable to wild-type transients, corroborating the preserved contractile function and suggesting that the compensatory mechanism lies in the Ca(2+)-induced Ca(2+) release event. We next functionally probed dyad structure, ryanodine receptor Ca(2+) sensitivity, and sarcoplasmic reticulum Ca(2+) load and found that increased temporal synchronicity of the Ca(2+) release in KChIP2(-/-) cardiomyocytes may reflect improved dyad structure aiding the compensatory mechanisms in preserving cardiac contractile force. Thus the bimodal effect of KChIP2 on Ito,f and ICa,L constitutes an important regulatory effect of KChIP2 on cardiac contractility, and we conclude that delayed repolarization and improved dyad structure function together to preserve cardiac contraction in KChIP2(-/-) mice.

U2 - 10.1152/ajpheart.00166.2015

DO - 10.1152/ajpheart.00166.2015

M3 - Journal article

VL - 309

SP - H481-H489

JO - American Journal of Physiology: Heart and Circulatory Physiology

JF - American Journal of Physiology: Heart and Circulatory Physiology

SN - 0363-6135

IS - 3

ER -

ID: 144206487