Triggered activity in atrial myocytes is influenced by Na+/Ca2+ exchanger activity in genetically altered mice
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Triggered activity in atrial myocytes is influenced by Na+/Ca2+ exchanger activity in genetically altered mice. / Bögeholz, N; Pauls, P; Kaese, S; Schulte, J S; Lemoine, M D; Dechering, D G; Frommeyer, G; Goldhaber, J I; Seidl, M D; Kirchhefer, U; Eckardt, L; Müller, F U; Pott, C.
In: J MOL CELL CARDIOL, Vol. 101, 12.2016, p. 106-115.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Triggered activity in atrial myocytes is influenced by Na+/Ca2+ exchanger activity in genetically altered mice
AU - Bögeholz, N
AU - Pauls, P
AU - Kaese, S
AU - Schulte, J S
AU - Lemoine, M D
AU - Dechering, D G
AU - Frommeyer, G
AU - Goldhaber, J I
AU - Seidl, M D
AU - Kirchhefer, U
AU - Eckardt, L
AU - Müller, F U
AU - Pott, C
N1 - Copyright © 2016 Elsevier Ltd. All rights reserved.
PY - 2016/12
Y1 - 2016/12
N2 - AIMS: In atrial fibrillation, increased function of the Na+/Ca2+-exchanger (NCX) is one among several electrical remodeling mechanisms.METHODS/RESULTS: Using the patch-clamp- and Ca2+ imaging-methods, we investigated atrial myocytes from NCX-homozygous-overexpressor (OE)- and heterozygous-knockout (KO)-mice and their corresponding wildtypes (WTOE; WTKO). NCX mediated Ca2+ extrusion capacity was reduced in KO and increased in OE. There was no evidence for structural or molecular remodeling. During a proarrhythmic pacing-protocol, the number of low amplitude delayed afterdepolarizations (DADs) was unaltered in OE vs. WTOE and KO vs. WTKO. However, DADs triggered full spontaneous action potentials (sAP) significantly more often in OE vs. WTOE (ratio sAP/DAD: OE:0.18±0.05; WTOE:0.02±0.02; p<0.001). Using the same protocol, a DAD triggered an sAP by tendency less often in KO vs. WTKO (p=0.06) and significantly less often under a more aggressive proarrhythmic protocol (ratio sAP/DAD: KO:0.01±0.003; WT KO: 0.12±0.05; p=0.007). The DAD amplitude was increased in OE vs. WTOE and decreased in KO vs. WTKO. There were no differences in SR-Ca2+-load, the number of spontaneous Ca2+-release-events or IKACh/IK1.CONCLUSIONS: Atrial myocytes with increased NCX expression exhibited increased vulnerability towards sAPs while atriomyocytes with reduced NCX expression were protected. The underlying mechanism consists of a modification of the DAD-amplitude by the level of NCX-activity. Thus, although the number of spontaneous Ca2+-releases and therefore DADs is unaltered, the higher DAD-amplitude in OE made a transgression of the voltage-threshold of an sAP more likely. These findings indicate that the level of NCX activity could influence triggered activity in atrial myocytes independent of possible remodeling processes.
AB - AIMS: In atrial fibrillation, increased function of the Na+/Ca2+-exchanger (NCX) is one among several electrical remodeling mechanisms.METHODS/RESULTS: Using the patch-clamp- and Ca2+ imaging-methods, we investigated atrial myocytes from NCX-homozygous-overexpressor (OE)- and heterozygous-knockout (KO)-mice and their corresponding wildtypes (WTOE; WTKO). NCX mediated Ca2+ extrusion capacity was reduced in KO and increased in OE. There was no evidence for structural or molecular remodeling. During a proarrhythmic pacing-protocol, the number of low amplitude delayed afterdepolarizations (DADs) was unaltered in OE vs. WTOE and KO vs. WTKO. However, DADs triggered full spontaneous action potentials (sAP) significantly more often in OE vs. WTOE (ratio sAP/DAD: OE:0.18±0.05; WTOE:0.02±0.02; p<0.001). Using the same protocol, a DAD triggered an sAP by tendency less often in KO vs. WTKO (p=0.06) and significantly less often under a more aggressive proarrhythmic protocol (ratio sAP/DAD: KO:0.01±0.003; WT KO: 0.12±0.05; p=0.007). The DAD amplitude was increased in OE vs. WTOE and decreased in KO vs. WTKO. There were no differences in SR-Ca2+-load, the number of spontaneous Ca2+-release-events or IKACh/IK1.CONCLUSIONS: Atrial myocytes with increased NCX expression exhibited increased vulnerability towards sAPs while atriomyocytes with reduced NCX expression were protected. The underlying mechanism consists of a modification of the DAD-amplitude by the level of NCX-activity. Thus, although the number of spontaneous Ca2+-releases and therefore DADs is unaltered, the higher DAD-amplitude in OE made a transgression of the voltage-threshold of an sAP more likely. These findings indicate that the level of NCX activity could influence triggered activity in atrial myocytes independent of possible remodeling processes.
KW - Action Potentials/genetics
KW - Animals
KW - Calcium/metabolism
KW - Calcium Signaling
KW - Female
KW - Gene Expression
KW - Heart Atria/metabolism
KW - Male
KW - Membrane Potentials/genetics
KW - Mice
KW - Mice, Transgenic
KW - Myocardial Contraction/genetics
KW - Myocardium/metabolism
KW - Myocytes, Cardiac/metabolism
KW - Sarcoplasmic Reticulum/metabolism
KW - Sodium-Calcium Exchanger/genetics
U2 - 10.1016/j.yjmcc.2016.11.004
DO - 10.1016/j.yjmcc.2016.11.004
M3 - SCORING: Journal article
C2 - 27838371
VL - 101
SP - 106
EP - 115
JO - J MOL CELL CARDIOL
JF - J MOL CELL CARDIOL
SN - 0022-2828
ER -
