Reduced volume-regulated outwardly rectifying anion channel activity in ventricular myocyte of type 1 diabetic mice

Yamamoto, Shintaro; Ichishima, Kunihiko; Ehara, Tsuguhisa

doi:10.1007/s12576-008-0012-8

Cited by 8 publications

(9 citation statements)

References 45 publications

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“…In HYPO without PE, the whole cell current gradually increased, reaching a steady level in about 15 min. This result is similar to the previous reports (Yamamoto et al ., 2008; 2009). In the presence of PE, exposure of the cells to HYPO increased the whole cell current only slightly.…”

Section: Resultssupporting

confidence: 94%

“…The current–voltage ( I‐V ) relationship of the HYPO‐induced current (difference current) showed a moderate outward rectification with the reversal potential ( E rev ) of about −20 mV (Figure 1B), a value close to the predicted Cl ‐ equilibrium potential ( E Cl =−21 mV) under the present condition ([Cl ‐ ] o /[Cl ‐ ] i = 105 mM/45 mM). These properties of the HYPO‐induced current appeared to match those reported for the VRAC current in mouse ventricular cells (Gong et al ., 2004; Yamamoto‐Mizuma et al ., 2004b; Yamamoto et al ., 2009). The mean‐ I‐V relationships of whole‐cell currents obtained in ISO and HYPO ( n = 15) are shown in Figure 1C.…”

Section: Resultsmentioning

confidence: 99%

“…The results obtained so far support the view that the increase in the whole cell current observed here in HYPO in mouse ventricular cells is due to the activation of VRAC current, as noted in the previous studies (Gong et al ., 2004; Yamamoto‐Mizuma et al ., 2004b; Yamamoto et al ., 2009). Subsequently, we designated the HYPO‐induced current as VRAC current.…”

Section: Resultsmentioning

confidence: 99%

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α₁‐Adrenoceptor‐mediated depletion of phosphatidylinositol 4, 5‐bisphosphate inhibits activation of volume‐regulated anion channels in mouse ventricular myocytes

Ichishima

Yamamoto

Iwamoto

et al. 2010

British J Pharmacology

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Volume-regulated anion channels (VRACs) play an important role in cell-volume regulation. a1-Adrenoceptor stimulation by phenylephrine (PE) suppressed the hypotonic activation of VRAC current in mouse ventricular cells and regulatory volume decrease (RVD) was also absent in PE-treated cells. We examined whether the effects of a1-adrenoceptor stimuli on VRAC current were modulated by phosphatidylinositol signalling. EXPERIMENTAL APPROACHWhole-cell patch-clamp method was used to record the hypotonicity-induced VRAC current in mouse ventricular cells. RVD was analyzed by videomicroscopic measurement of cell images. KEY RESULTSThe attenuation of VRAC current by PE was suppressed by a1A-adrenoceptor antagonists (prazosin and WB-4101), anti-Gq protein antibody and a specific phosphoinositide-specific phospholipase C (PLC) inhibitor (U-73122), but not by antagonists for a1B-, a1D-or b-adrenoceptor, or protein kinase C inhibitors. The inhibition of VRAC by PE was antagonized by intracellular excess phosphatidylinositol 4,5-bisphosphate (PIP2), while intracellular anti-PIP2 antibody (PIP2 Ab) inhibited the activation of VRAC currents. When cells were loaded with phosphatidylinositol 3,4,5-trisphosphate (PIP3) with or without PIP2 Ab, PE little affected the VRAC current. Extracellular m-3M3FBS (an activator of PLC) suppressed VRAC in the absence of PE, and this effect was reversed by intracellular excess PIP2. CONCLUSIONS AND IMPLICATIONSOur results indicate that the stimulation of a1A-adrenoceptors by PE inhibited the activation of cardiac VRAC current via PIP3 depletion brought about by PLC-dependent reduction of membrane PIP2 level.

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Section: Resultssupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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α₁‐Adrenoceptor‐mediated depletion of phosphatidylinositol 4, 5‐bisphosphate inhibits activation of volume‐regulated anion channels in mouse ventricular myocytes

Ichishima

Yamamoto

Iwamoto

et al. 2010

British J Pharmacology

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“…Inhibition of VRAC was shown in cells with intracellular application of LY294002 (a PI3K inhibitor) or anti-PIP2 antibody. PIP3, but not PIP2, restored the VRAC current suppressed by LY294002 or anti-PIP2 antibody, whereas intracellular PIP3 or PIP2 influenced neither the basal background current in isotonic solution nor the VRAC current in hypotonic solution (24). According to these results, we hypothesize that two distinct steps are required for VRAC activation.…”

Section: +mentioning

confidence: 66%

New Molecular Mechanisms for Cardiovascular Disease: Cardiac Hypertrophy and Cell-Volume Regulation

et al. 2011

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Abstract. Cardiac hypertrophy is an increase in the muscle volume of the ventricle due to the enlargement of cardiac cells. Physiological cardiac hypertrophy is the normal response to healthy exercise, and pathological hypertrophy is the response to increased stress such as hypertension. Intracellular and extracellular aniosmotic conditions also change cell volume. Since persistent cell swelling or cell shrinkage during aniosmotic conditions results in cell death, the ability to regulate cell volume is important for the maintenance of cellular homeostasis. Cell swelling activates a regulatory volume decrease (RVD) response in which solute leakage pathways are stimulated and solute with water exits cells, reducing the cell volume towards the original value. In cardiac cells, one of the essential factors for cell-volume regulation is the volume-regulated anion channel (VRAC). However, the relationship between cardiac hypertrophy and cell-volume regulation is not clear. In this review, we introduce our recent findings showing that the impairment of VRAC current is exhibited in ventricular cells from mice with cardiac hypertrophy induced by transverse aortic constriction. Similar results were shown in caveolin-3-deficient mice, which develop cardiac hypertrophy without pressure overload. These results suggest that VRAC will be a new target for protection from the development of cardiac hypertrophy.

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“…Single ventricular cells from mice (18-25 g, C-57BL/6J/ black inbred, male) anaesthetised with sodium pentobarbitone (50 mg/mL, I.P.) were isolated by an enzymatic dispersion technique (20). The stock and A two-tailed probability of < 0.05 indicated statistical significance.…”

mentioning

confidence: 99%

OSU-03012, a novel celecoxib derivative, induces cell swelling and shortens action potential duration in mouse ventricular cells

Yamamoto¹,

Iyoda²,

Kita³

et al. 2010

Biomed. Res.

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OSU03012, a novel celecoxib derivative, has been shown to inhibit proliferation and induce apoptosis in numerous cancer cell lines. However, not much is known about its influence on cell volume regulation and cardiac function in the mammalian heart. We examined the effects of OSU-03012 on cell volume and action potentials in mouse ventricular cells. Video image analysis showed that cell volume increased on application of OSU-03012 in a dose-dependent manner. The action potential duration (APD) at 50% and 90% repolarization (APD 50 and APD 90 respectively) as well as the resting membrane potential (RMP) were measured in current-clamp experiments. OSU-03012 had little effect on APD 50 and RMP but induced approximately 30% shortening of APD 90 . These results for cell volume and AP are similar to those in cells under ischaemia/hypoxia, and we confirmed that the shortening of APD 90 was almost completely recovered by glibenclamide, a potent inhibitor of ATP-sensitive potassium channels. We concluded that OSU-03012 may lead to cell swelling and shortening of AP via reduced ATP production in mouse ventricular cells.OSU-03012 has been shown to be a potent phosphoinositide-dependent kinase-1 (PDK1) inhibitor derived from the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib, but it does not possess COX-2 inhibitory activity (10,22). Celecoxib is used for preventing an increase in the number of cancer cells, which may be due to moderate apoptosis through blocking of PDK1/Akt signalling (22). OSU-03012 was shown to be a more potent inhibitor of cancer cell growth than celecoxib, and it inhibited both recombinant PDK1 activity and PC-3 cell viability with IC 50 values of about 5 μM (22). This new compound is currently undergoing preclinical development under the Rapid Access to Intervention Development Program at the National Cancer Institute. Until date, several mechanisms have been reported for OSO-03012-induced cell death. Zhang et al. (21) showed that the loss of mitochondrial membrane potential may be involved in OSU-03012-induced cell death in multiple myeloma cells. Furthermore, genomic inhibition of PDK1 was reported to suppress cardiac functions in the mouse heart (3, 8, 11), however, severe cardiac side effects of OSU-03012 were not reported at blood concentrations below 20 μM (6, 15). To our knowledge, information on direct effects of OSU-03012 on cardiac function is absent. In the present study, we examined the effect of OSU-03012 on cardiac cell volume and action potential (AP) in an attempt to elucidate the effect of this compound on cardiac function. Fukuoka University Animal Care and Use Committee approved the use and treatment of all animals included in the experiments described here. Single ventricular cells from mice (18-25 g, C-57BL/6J/ black inbred, male) anaesthetised with sodium pentobarbitone (50 mg/mL, I.P.) were isolated by an enzymatic dispersion technique (20). The stock and A two-tailed probability of < 0.05 indicated statistical significance. Figure 1A and B represent typical vi...

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Reduced volume-regulated outwardly rectifying anion channel activity in ventricular myocyte of type 1 diabetic mice

Cited by 8 publications

References 45 publications

α₁‐Adrenoceptor‐mediated depletion of phosphatidylinositol 4, 5‐bisphosphate inhibits activation of volume‐regulated anion channels in mouse ventricular myocytes

α₁‐Adrenoceptor‐mediated depletion of phosphatidylinositol 4, 5‐bisphosphate inhibits activation of volume‐regulated anion channels in mouse ventricular myocytes

New Molecular Mechanisms for Cardiovascular Disease: Cardiac Hypertrophy and Cell-Volume Regulation

OSU-03012, a novel celecoxib derivative, induces cell swelling and shortens action potential duration in mouse ventricular cells

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Reduced volume-regulated outwardly rectifying anion channel activity in ventricular myocyte of type 1 diabetic mice

Cited by 8 publications

References 45 publications

α1‐Adrenoceptor‐mediated depletion of phosphatidylinositol 4, 5‐bisphosphate inhibits activation of volume‐regulated anion channels in mouse ventricular myocytes

α1‐Adrenoceptor‐mediated depletion of phosphatidylinositol 4, 5‐bisphosphate inhibits activation of volume‐regulated anion channels in mouse ventricular myocytes

New Molecular Mechanisms for Cardiovascular Disease: Cardiac Hypertrophy and Cell-Volume Regulation

OSU-03012, a novel celecoxib derivative, induces cell swelling and shortens action potential duration in mouse ventricular cells

Contact Info

Product

Resources

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α₁‐Adrenoceptor‐mediated depletion of phosphatidylinositol 4, 5‐bisphosphate inhibits activation of volume‐regulated anion channels in mouse ventricular myocytes

α₁‐Adrenoceptor‐mediated depletion of phosphatidylinositol 4, 5‐bisphosphate inhibits activation of volume‐regulated anion channels in mouse ventricular myocytes