The Expression, Phosphorylation, and Localization of Connexin 43 and Gap-Junctional Intercellular Communication during the Establishment of a Synchronized Contraction of Cultured Neonatal Rat Cardiac Myocytes

Oyamada, Masahito; Kimura, Hisakazu; Oyamada, Yumiko; Miyamoto, Atsushi; Ohshika, Hideyo; Mori, Makoto

doi:10.1006/excr.1994.1154

Cited by 89 publications

(66 citation statements)

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“…26,27 In contrast with previous reports, the present study found that the out that the continuous asynchronous contraction and relaxation of damaged myocardium could result in poor heart function. Thus, the enhancement of contractility observed in the present study was probably due to the improvement of myocardial systolic-diastolic co-ordination.…”

Section: Poly(n-isopropylacrylamide) Hydrogel For Cardiac Protectioncontrasting

confidence: 99%

Physical Properties of Poly (N-isopropylacrylamide) Hydrogel Promote its Effects on Cardiac Protection after Myocardial Infarction

Ren¹,

Jiang²,

et al. 2012

J Int Med Res

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Section: Poly(n-isopropylacrylamide) Hydrogel For Cardiac Protectioncontrasting

confidence: 99%

Physical Properties of Poly (N-isopropylacrylamide) Hydrogel Promote its Effects on Cardiac Protection after Myocardial Infarction

Ren¹,

Jiang²,

et al. 2012

J Int Med Res

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“…In the uterus, as in cardiac muscle and vascular smooth muscle, functional gap junctions promote the development of coordinated oscillatory contractions (Garfield and Hayashi, 1981;Christ et al, 1993;Oyamada et al, 1994;Watts et al, 1994;Tsai et al, 1995;Delorme et al, 1997). Lindane inhibits gap junction communication between myometrial cells in culture and inhibits spontaneous oscillatory contractions of uterine strips in muscle baths, as shown previously Loch-Caruso, 1995, 1999; and confirmed in the present report.…”

Section: Discussionsupporting

confidence: 89%

Phospholipase-Mediated Inhibition of Spontaneous Oscillatory Uterine Contractions by Lindane in Vitro,

Wang

Loch‐Caruso

2002

Toxicology and Applied Pharmacology

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Although regulation of uterine contractility is fundamental for parturition, mechanisms by which toxicants modify uterine muscle contractions remain poorly understood. In a previous cumulative concentration-response study, 10 μM lindane (γ-hexachlorocyclohexane) reduced contraction force and 30 μM lindane abolished contractions in Gestation Day 10 rat uterine strips when lindane was added to muscle baths at 10-min intervals. Other studies showed that brief (<10 min) exposures to 10-100 μM lindane inhibit gap junctions and activate phospholipase pathways in rat myometrial cells in culture. Consequently, lindane was used as a prototype toxicant with known uterine activity to investigate the hypothesis that activation of a specific phospholipase pathway provides a mechanistic link between inhibition of uterine contraction and inhibition of myometrial gap junctions. Uterine tissue and cells were pretreated with phospholipase pathway inhibitors to evaluate the role of phospholipase pathways in lindane's actions in the uterus. Concentrations of inhibitors were selected based on previous reports of effective concentrations for the enzyme activity and on pilot toxicity studies of the inhibitors on uterine contraction and gap junction communication. To monitor uterine contractions, longitudinal uterine strips were excised from Gestation Day 10 rats and suspended in isometric muscle baths, consistent with previous experiments. Exposure in vitro for 60 min to 10-50 μM lindane, an effective concentration range for the uterine responses of interest, revealed that 30 μM lindane rapidly abolished contractions. Subsequently, uterine strips were pretreated with phospholipase pathway inhibitors and then challenged with 30 μM lindane, the lindane concentration that elicited maximal inhibition of uterine contraction. Pretreatment with 20-50 μM of the phosphatidylinositol-specific phospholipase C inhibitor 1-O-octadecyl-2-O-methyl-sn -glycerol-3-phosphorylcholine (ET-18-OCH 3 ) reversed lindane-induced inhibition of spontaneous uterine contractions. Gap junction intercellular communication was monitored by injecting the fluorescent dye Lucifer yellow into rat myometrial cells grown in culture and assessing dye transfer to adjacent cells using epifluorescence microscopy. Similar to uterine contraction, pretreatment of cell cultures with phospholipase C inhibitors (30 μM ET-18-OCH 3 , 50 μM tricyclodecan-p-yl-xanthogenate · K [D609] or 50 μM tricyclodecan-p-yl-xanthogenate · K or 2-nitro-4-carboxyphenyl-N,Ndophenylcarbamate [NCDC]) partially reversed inhibition of dye transfer by 100 μM lindane, a 4To whom correspondence and reprint requests should be addressed at 1420 Washington Heights, Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2029. Fax: (734) lindane concentration previously shown to abolish myometrial Lucifer yellow dye transfer under similar culture conditions. In contrast, pretreatment with 20 μM of bromoenol lactone (BEL) to inhibit the calcium-i...

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“…4,32 Considering the myocardium as an electromechanical syncytium, electrical heterogeneity and disrupted wave front propagation could in turn lead to uncoordinated myocyte contraction and diminish ventricular contractile force. Our study demonstrated the progressive remodeling of myocardial Cx43 and corresponding impairment of systolic function, along with the slowing of CV, suggesting the linkage between gap junction and cardiac contractility.…”

Section: Discussionmentioning

confidence: 99%

Downregulated myocardial connexin 43 and suppressed contractility in rabbits subjected to a cholesterol-enriched diet

Lin

Yeh

et al. 2005

Laboratory Investigation

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The effects of hypercholesterolemia on the myocardium per se include electrophysiological and mechanical alterations. Since gap junctions are essential in electromechanical coupling throughout the heart, we examined the correlation between the temporal expression of cardiac connexin 43 (Cx43), contractile function, and conduction velocity in cholesterol-fed rabbits. After a 12-week feeding period, serum cholesterol levels gradually increased (Po0.001). In contrast, expression of cardiomyocyte Cx43 protein progressively decreased (60% reduction at 12 weeks, Po0.001). Such a reduction was also demonstrated by immunoconfocal microscopy, which further showed redistribution of Cx43 gap junctions at the lateral cell membrane. The downregulation of Cx43 protein was associated with increased levels of Cx43 mRNA (3.5 -fold at 12 weeks, Po0.001) and phosphorylated c-Jun N-terminal kinase (three-fold at 12 weeks, P ¼ 0.001). Functionally, although fractional shortening of the left ventricle remained unchanged throughout the feeding protocol, the cholesterol-fed rabbits had a reduced cardiac cycle-dependent variation of integrated backscatters, a decreased mitral ring systolic velocity, and an increased modified Tei index (all Po0.001), all of which indicated impaired intrinsic myocardial contractility and attenuated ventricular systolic performance. In Langendorff-perfused hearts of cholesterol-fed rabbits, decreased conduction velocity was observed (Po0.005). Withdrawal of the cholesterol-enriched diet for 18 weeks restored the contractile parameters and Cx43 protein expression. These findings suggest that Cx43 is highly involved in the molecular mechanism of hypercholesterolemia-induced cardiac contractile dysfunction and dysrhythmias.

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The Expression, Phosphorylation, and Localization of Connexin 43 and Gap-Junctional Intercellular Communication during the Establishment of a Synchronized Contraction of Cultured Neonatal Rat Cardiac Myocytes

Cited by 89 publications

References 0 publications

Physical Properties of Poly (N-isopropylacrylamide) Hydrogel Promote its Effects on Cardiac Protection after Myocardial Infarction

Physical Properties of Poly (N-isopropylacrylamide) Hydrogel Promote its Effects on Cardiac Protection after Myocardial Infarction

Phospholipase-Mediated Inhibition of Spontaneous Oscillatory Uterine Contractions by Lindane in Vitro,

Downregulated myocardial connexin 43 and suppressed contractility in rabbits subjected to a cholesterol-enriched diet

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