Effect of transient elevation of glucose on contractile properties in non-diabetic rat cardiac muscle

Miura, Makoto; Hasegawa, Takehisa; Matsumoto, Akinobu; Nishiyama, M; Someya, Yuka; Satoh, Wataru; Kumasaka, Kazunori; Shindoh, Chiyohiko; Sato, Haruka

doi:10.1007/s00380-020-01726-6

Cited by 4 publications

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“…The resulting offspring, Gja1 ox/ ox / Myh6-cre +/mice (cCx43 -/mice) and their littermates (cCx43 +/+ mice) were used for experiments (Figure S1A) [41]. Cx43 was expressed in the inner mitochondrial membrane of cCx43 +/+ mice, but not in that of cCx43 -/mice (Figure S1B) Measurements of force, rhod-2 uorescence, and MitoTracker Green uorescence in mouse trabeculae After mice had been adequately anesthetized with intraperitoneal injection of butorphanol tartrate (2.5 mg/kg), midazolam (2 mg/kg), and medetomidine chloride (0.15 mg/kg), trabeculae were dissected from the right ventricles of their hearts (Figure S1C) [23,24,35,41]. Removal of the hearts for dissection resulted in euthanasia.…”

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confidence: 99%

Mitochondrial connexin43 and mitochondrial KATP channels modulate triggered arrhythmias in mouse ventricular muscle

Sato

Nishiyama

Morita

et al. 2023

Pflugers Arch - Eur J Physiol

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Aim: Connexin43 (Cx43) exits as hemichannels in the inner mitochondrial membrane. We examined how mitochondrial Cx43 and mitochondrial KATP channels affect the occurrence of triggered arrhythmias.Methods and Results: To generate cardiac-speci c Cx43-de cient (cCx43-/-) mice, Cx43 ox/ ox mice were crossed with α-MHC (Myh6)-cre+/-mice. The resulting offspring, Cx43 ox/ ox/ Myh6-cre+/mice (cCx43-/-mice) and their littermates (cCx43+/+ mice), were used. Trabeculae were dissected from right ventricles of mouse hearts. Cardiomyocytes were enzymatically isolated from ventricles of mouse hearts. Force was measured with a strain gauge in trabeculae (22°C). To assess arrhythmia susceptibility, the minimal extracellular Ca2+ concentration ([Ca2+]o,min), at which arrhythmias were induced by electrical stimulation, was determined in trabeculae. ROS production was estimated with 2',7'-dichloro uorescein (DCF), mitochondrial membrane potential with tetramethylrhodamine methylester(TMRM), and Ca2+ spark frequency with uo-4 and confocal microscopy in cardiomyocytes. Mitochondrial Ca2+ was estimated with rhod-2 in trabeculae. Diazoxide was used to open mitochondrial KATP. Most of cCx43-/mice died suddenly within 8 weeks. Cx43 was present in the inner mitochondrial membrane in cCx43+/+mice, but not in cCx43-/-mice. In cCx43-/mice, the [Ca2+]o,min was lower, Ca2+ spark frequency and DCF oxidation rate were more increased, and TMRM uorescence was more decreased. These changes in cCx43-/-mice were suppressed by diazoxide. Besides, in cCx43-/mice, antioxidant peptide SS-31 increased the [Ca2+]o,min. Rhod-2 uorescence was increased at high [Ca2+]o only in Cx43-/mice.Conclusions: These results suggest that the de ciency of Cx43 activates Ca2+ leak from the SR probably due to an increase in ROS production, depolarization of mitochondrial membrane potential, and an increase in mitochondrial Ca2+, thereby causing triggered arrhythmias and that the de ciency of Cx43 hemichannels may be compensated by activation of mitochondrial KATP channels in mouse hearts.

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