The Experts below are selected from a list of 16593 Experts worldwide ranked by ideXlab platform
Sebastian Albinsson - One of the best experts on this subject based on the ideXlab platform.
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Spontaneous activity and stretch-induced contractile differentiation are reduced in vascular smooth muscle of miR-143/145 knockout mice.
Acta physiologica (Oxford England), 2015Co-Authors: Anirban Bhattachariya, Diana Dahan, Mari Ekman, Thomas Boettger, Thomas Braun, Karl Swärd, Per Hellstrand, Sebastian AlbinssonAbstract:Stretch is essential for maintaining the contractile phenotype of vascular smooth muscle cells, and small non-coding microRNAs are known to be important in this process. Using a Dicer knockout model, we have previously reported that microRNAs are essential for stretch-induced differentiation and regulation of L-type Calcium Channel Expression. The aim of this study was to investigate the importance of the smooth muscle-enriched miR-143/145 microRNA cluster for stretch-induced differentiation of the portal vein.
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Regulation of vascular smooth muscle mechanotransduction by microRNAs and L-type Calcium Channels.
Communicative & integrative biology, 2013Co-Authors: Karolina M. Turczyńska, Karl Swärd, Per Hellstrand, Sebastian AlbinssonAbstract:The phenotype of smooth muscle cells is regulated by multiple environmental factors including mechanical forces. Mechanical stretch of mouse portal veins ex vivo has been shown to promote contractile differentiation by activation of the Rho-pathway, an effect that is dependent on the influx of Calcium via L-type Calcium Channels. MicroRNAs have recently been demonstrated to play a significant role in the control of smooth muscle phenotype and in a recent report we investigated their role in vascular mechanosensing. By smooth muscle specific deletion of Dicer, we found that microRNAs are essential for smooth muscle differentiation in response to stretch by regulating CamKIIδ and L-type Calcium Channel Expression. Furthermore, we suggest that loss of L-type Calcium Channels in Dicer KO is due to reduced Expression of the smooth muscle-enriched microRNA, miR-145, which targets CamKIIδ. These results unveil a novel mechanism for miR-145 dependent regulation of smooth muscle phenotype.
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MicroRNAs are essential for stretch-induced vascular smooth muscle contractile differentiation via miR-145-dependent Expression of L-type Calcium Channels
The Journal of biological chemistry, 2012Co-Authors: Karolina M. Turczyńska, Karl Swärd, Per Hellstrand, Mardjaneh Karbalaei Sadegh, Sebastian AlbinssonAbstract:Abstract Stretch of the vascular wall is an important stimulus to maintain smooth muscle contractile differentiation that is known to depend on L-type Calcium influx, Rho-activation, and actin polymerization. The role of microRNAs in this response was investigated using tamoxifen-inducible and smooth muscle-specific Dicer KO mice. In the absence of Dicer, which is required for microRNA maturation, smooth muscle microRNAs were completely ablated. Stretch-induced contractile differentiation and Rho-dependent cofilin-2 phosphorylation were dramatically reduced in Dicer KO vessels. On the other hand, acute stretch-sensitive growth signaling, which is independent of influx through L-type Calcium Channels, was not affected by Dicer KO. Contractile differentiation induced by the actin polymerizing agent jasplakinolide was not altered by deletion of Dicer, suggesting an effect upstream of actin polymerization. Basal and stretch-induced L-type Calcium Channel Expressions were both decreased in Dicer KO portal veins, and inhibition of L-type Channels in control vessels mimicked the effects of Dicer deletion. Furthermore, inhibition of miR-145, a highly expressed microRNA in smooth muscle, resulted in a similar reduction of L-type Calcium Channel Expression. This was abolished by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN93, suggesting that Ca2+/calmodulin-dependent protein kinase IIδ, a target of miR-145 and up-regulated in Dicer KO, plays a role in the regulation of L-type Channel Expression. These results show that microRNAs play a crucial role in stretch-induced contractile differentiation in the vascular wall in part via miR-145-dependent regulation of L-type Calcium Channels.
Michel F. Rossier - One of the best experts on this subject based on the ideXlab platform.
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MicroRNA-204 Is Necessary for Aldosterone-Stimulated T-Type Calcium Channel Expression in Cardiomyocytes
International journal of molecular sciences, 2018Co-Authors: Riko Koyama, Michel F. Rossier, Tiphaine Mannic, Jumpei Ito, Laurence Amar, Maria-christina Zennaro, Andrés D. MaturanaAbstract:Activation of the mineralocorticoid receptor (MR) in the heart is considered to be a cardiovascular risk factor. MR activation leads to heart hypertrophy and arrhythmia. In ventricular cardiomyocytes, aldosterone induces a profound remodeling of ion Channel Expression, in particular, an increase in the Expression and activity of T-type voltage-gated Calcium Channels (T-Channels). The molecular mechanisms immediately downstream from MR activation, which lead to the increased Expression of T-Channels and, consecutively, to an acceleration of spontaneous cell contractions in vitro, remain poorly investigated. Here, we investigated the putative role of a specific microRNA in linking MR activation to the regulation of T-Channel Expression and cardiomyocyte beating frequency. A screening assay identified microRNA 204 (miR-204) as one of the major upregulated microRNAs after aldosterone stimulation of isolated neonatal rat cardiomyocytes. Aldosterone significantly increased the level of miR-204, an effect blocked by the MR antagonist spironolactone. When miR-204 was overexpressed in isolated cardiomyocytes, their spontaneous beating frequency was significantly increased after 24 h, like upon aldosterone stimulation, and messenger RNAs coding T-Channels (CaV3.1 and CaV3.2) were increased. Concomitantly, T-type Calcium currents were significantly increased upon miR-204 overExpression. Specifically repressing the Expression of miR-204 abolished the aldosterone-induced increase of CaV3.1 and CaV3.2 mRNAs, as well as T-type Calcium currents. Finally, aldosterone and miR-204 overExpression were found to reduce REST-NRSF, a known transcriptional repressor of CaV3.2 T-type Calcium Channels. Our study thus strongly suggests that miR-204 Expression stimulated by aldosterone promotes the Expression of T-Channels in isolated rat ventricular cardiomyocytes, and therefore, increases the frequency of the cell spontaneous contractions, presumably through the inhibition of REST-NRSF protein.
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DHEA Prevents Mineralo- and Glucocorticoid Receptor-Induced Chronotropic and Hypertrophic Actions in Isolated Rat Cardiomyocytes
Endocrinology, 2013Co-Authors: Tiphaine Mannic, Andrés D. Maturana, Mounira Mouffok, Magaly Python, Takehisa Yoshida, Nicolas Vuilleumier, Michel F. RossierAbstract:Corticosteroids have been involved in the genesis of ventricular arrhythmias associated with pathological heart hypertrophy, although molecular mechanisms responsible for these effects have not been completely explained. Because mineralocorticoid receptor (MR) antagonists have been demonstrated to be beneficial on the cardiac function, much attention has been given to the action of aldosterone on the heart. However, we have previously shown that both aldosterone and corticosterone in vitro induce a marked acceleration of the spontaneous contractions, as well as a significant cell hypertrophy in isolated neonate rat ventricular cardiomyocytes. Moreover, a beneficial role of the steroid hormone dehydroepiandrosterone (DHEA) has been also proposed, but the mechanism of its putative cardioprotective function is not known. We found that DHEA reduces both the chronotropic and the hypertrophic responses of cardiomyocytes upon stimulation of MR and glucocorticoid receptor (GR) in vitro. DHEA inhibitory effects were accompanied by a decrease of T-type Calcium Channel Expression and activity, as assessed by quantitative PCR and the patch-clamp technique. Prevention of cell hypertrophy by DHEA was also revealed by measuring the Expression of A-type natriuretic peptide and BNP. The kinetics of the negative chronotropic effect of DHEA, and its sensitivity to actinomycin D, pointed out the presence of both genomic and nongenomic mechanisms of action. Although the genomic action of DHEA was effective mostly upon MR activation, its rapid, nongenomic response appeared related to DHEA antioxidant properties. On the whole, these results suggest new mechanisms for a putative cardioprotective role of DHEA in corticosteroid-associated heart diseases.
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Aldosterone increases T-type Calcium Channel Expression and in vitro beating frequency in neonatal rat cardiomyocytes.
Cardiovascular research, 2005Co-Authors: Nathalie Lalevée, Michela Rebsamen, Stéphanie Barrère-lemaire, Emeline Perrier, Joël Nargeot, Jean-pierre Benitah, Michel F. RossierAbstract:Objective : Although aldosterone has been implicated in the pathogenesis of cardiac hypertrophy and heart failure, its cellular mechanism of action on cardiomyocyte function is not yet completely elucidated. This study was designed to investigate the effect of aldosterone on Calcium Channel Expression and cardiomyocyte contraction frequency. Methods : Cultured neonatal rat ventricular cardiomyocytes were stimulated in vitro with 1 μmol/L aldosterone for 24 h. Calcium currents were then measured with the patch clamp technique, while Calcium Channel Expression was assessed by real-time RT-PCR. Results : In the present study, we show that aldosterone increases Ca2+ currents by inducing Channel Expression. Indeed, aldosterone led to a substantial increase of L- and T-type Ca2+ current amplitudes, and we found a concomitant 55% increase of the mRNA coding for α1C and β2 subunits of cardiac L Channels. Although T-type currents were relatively small under control conditions, they increased 4-fold and T Channel α1H isoform Expression rose in the same proportion after aldosterone treatment. Because T Channels have been implicated in the modulation of membrane electrical activity, we investigated whether aldosterone affects the beating frequency of isolated cardiomyocytes. In fact, aldosterone dose-dependently increased the spontaneous beating frequency more than 4-fold. This effect of aldosterone was prevented by actinomycin D and spironolactone and reduced by RU486, suggesting a mixed mineralocorticoid/glucocorticoid receptor-dependent transcriptional mechanism. Moreover, inhibition of T currents with Ni2+ or mibefradil significantly reduced beating frequency towards control values, while conditions affecting L-type currents completely blocked contractions. Conclusion : Aldosterone modulates the Expression of cardiac voltage-operated Ca2+ Channels and accelerates beating in cultured neonatal rat ventricular myocytes. This chronotropic action of aldosterone appears to be linked to increased T Channel activity and could contribute to the deleterious effect of an excess of this steroid in vivo on cardiac function.
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Rapid communication Aldosterone increases T-type Calcium Channel Expression and in vitro beating frequency in neonatal rat cardiomyocytes
2005Co-Authors: Michela Rebsamen, Emeline Perrier, Michel F. RossierAbstract:Objective: Although aldosterone has been implicated in the pathogenesis of cardiac hypertrophy and heart failure, its cellular mechanism of action on cardiomyocyte function is not yet completely elucidated. This study was designed to investigate the effect of aldosterone on Calcium Channel Expression and cardiomyocyte contraction frequency. Methods: Cultured neonatal rat ventricular cardiomyocytes were stimulated in vitro with 1 Amol/L aldosterone for 24 h. Calcium currents were then measured with the patch clamp technique, while Calcium Channel Expression was assessed by real-time RT-PCR. Results: In the present study, we show that aldosterone increases Ca 2+ currents by inducing Channel Expression. Indeed, aldosterone led to a substantial increase of L- and T-type Ca 2+ current amplitudes, and we found a concomitant 55% increase of the mRNA coding for a1C and h2 subunits of cardiac L Channels. Although T-type currents were relatively small under control conditions, they increased 4-fold and T Channel a1H isoform Expression rose in the same proportion after aldosterone treatment. Because T Channels have been implicated in the modulation of membrane electrical activity, we investigated whether aldosterone affects the beating frequency of isolated cardiomyocytes. In fact, aldosterone dose-dependently increased the spontaneous beating frequency more than 4-fold. This effect of aldosterone was prevented by actinomycin D and spironolactone and reduced by RU486, suggesting a mixed mineralocorticoid/glucocorticoid receptor-dependent transcriptional mechanism. Moreover, inhibition of T currents with Ni 2+ or mibefradil significantly reduced beating frequency towards control values, while conditions affecting L-type currents completely blocked contractions. Conclusion: Aldosterone modulates the Expression of cardiac voltage-operated Ca 2+ Channels and accelerates beating in cultured neonatal rat ventricular myocytes. This chronotropic action of aldosterone appears to be linked to increased T Channel activity and could contribute to the deleterious effect of an excess of this steroid in vivo on cardiac function.
Kenneth Takeda - One of the best experts on this subject based on the ideXlab platform.
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voltage dependent currents and modulation of Calcium Channel Expression in zona fasciculata cells from rat adrenal gland
The Journal of Physiology, 1995Co-Authors: J G Barbara, Kenneth TakedaAbstract:1. Whole-cell voltage-activated currents from single zona fasciculata (ZF) cells from rat adrenal glands were studied. T- and L-type Ca2+ currents and a slowly inactivating A-type K+ current were the three major currents observed. 2. In freshly isolated cells, the A-type K+ current and the T-type Ca2+ current were predominant. The A-type current was activated at -50 mV and inhibited by 4-amino-pyridine with a half-maximal block (IC50) at 130 microM while the T-type current was activated at -70 mV and blocked by Cd2+, Ni2+ and amiloride with IC50 values of 24.1, 132.4 and 518.9 microM, respectively. 3. Under current clamp, depolarizing current pulses produced a single Ca2+ action potential with Cs+ in the pipette internal solution. Upon replacement of Cs+ by K+, the half-amplitude width of the action potential was shortened and membrane potential oscillations were seen after the spike. 4. In freshly isolated cells and during the first 24 h after plating, the T-type current was observed in all cells, with L-type current being observed in 2 days in culture, (+)SDZ 202,791 potentiated L-type current by 407 +/- 12% and the antagonist (-)SDZ 202,791 blocked this increase. The L-type current was activated between -30 and -20 mV and was sensitive to nitrendipine and omega-conotoxin GVIA. 5. Pre-incubation of cultured ZF cells with adrenocorticotrophic hormone (ACTH) or vasoactive intestinal peptide (VIP) for 3 days resulted in a high, sustained level of Expression of T-type current, with a mean amplitude of 34.2 +/- 5.5 pA pF-1 for ACTH-treated cells compared with 3.4 +/- 1.8 pA pF-1 for untreated cells. Cycloheximide strongly inhibited this effect. Neither treatment affected L-type current Expression. 6. The Expression of both Ca2+ current types was unaffected by pre-incubation with 8-bromo-cAMP or forskolin. The protein kinase A antagonist, H89, did not inhibit the ACTH-induced upregulation of T-type Ca2+ currents. 7. It is concluded that the main voltage-dependent currents involved in cell excitability and steroidogenesis in rat adrenal ZF cells are an A-type K+ current and a T-type Ca2+ current. The physiological role and control of Expression of L-type Ca2+ Channels in rat ZF cells remain less clear.
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Voltage-dependent currents and modulation of Calcium Channel Expression in zona fasciculata cells from rat adrenal gland.
The Journal of physiology, 1995Co-Authors: J G Barbara, Kenneth TakedaAbstract:1. Whole-cell voltage-activated currents from single zona fasciculata (ZF) cells from rat adrenal glands were studied. T- and L-type Ca2+ currents and a slowly inactivating A-type K+ current were the three major currents observed. 2. In freshly isolated cells, the A-type K+ current and the T-type Ca2+ current were predominant. The A-type current was activated at -50 mV and inhibited by 4-amino-pyridine with a half-maximal block (IC50) at 130 microM while the T-type current was activated at -70 mV and blocked by Cd2+, Ni2+ and amiloride with IC50 values of 24.1, 132.4 and 518.9 microM, respectively. 3. Under current clamp, depolarizing current pulses produced a single Ca2+ action potential with Cs+ in the pipette internal solution. Upon replacement of Cs+ by K+, the half-amplitude width of the action potential was shortened and membrane potential oscillations were seen after the spike. 4. In freshly isolated cells and during the first 24 h after plating, the T-type current was observed in all cells, with L-type current being observed in < 2% of cells, even in the presence of (+)SDZ 202,791, a dihydropyridine Ca2+ Channel agonist. With time in culture, the T-type current disappeared, and a high-voltage-activated L-type current became increasingly apparent. In cells tested after > 2 days in culture, (+)SDZ 202,791 potentiated L-type current by 407 +/- 12% and the antagonist (-)SDZ 202,791 blocked this increase. The L-type current was activated between -30 and -20 mV and was sensitive to nitrendipine and omega-conotoxin GVIA. 5. Pre-incubation of cultured ZF cells with adrenocorticotrophic hormone (ACTH) or vasoactive intestinal peptide (VIP) for 3 days resulted in a high, sustained level of Expression of T-type current, with a mean amplitude of 34.2 +/- 5.5 pA pF-1 for ACTH-treated cells compared with 3.4 +/- 1.8 pA pF-1 for untreated cells. Cycloheximide strongly inhibited this effect. Neither treatment affected L-type current Expression. 6. The Expression of both Ca2+ current types was unaffected by pre-incubation with 8-bromo-cAMP or forskolin. The protein kinase A antagonist, H89, did not inhibit the ACTH-induced upregulation of T-type Ca2+ currents. 7. It is concluded that the main voltage-dependent currents involved in cell excitability and steroidogenesis in rat adrenal ZF cells are an A-type K+ current and a T-type Ca2+ current. The physiological role and control of Expression of L-type Ca2+ Channels in rat ZF cells remain less clear.
Jeffrey J. Clare - One of the best experts on this subject based on the ideXlab platform.
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The novel product of a five‐exon stargazin‐related gene abolishes CaV2.2 Calcium Channel Expression
The EMBO journal, 2002Co-Authors: Fraser J. Moss, Patricia Viard, Anthony Davies, Federica Bertaso, Karen M. Page, Alex Graham, C Canti, Mary Plumpton, Christopher Plumpton, Jeffrey J. ClareAbstract:We have cloned and characterized a new member of the voltage-dependent Ca2+ Channel γ subunit family, with a novel gene structure and striking properties. Unlike the genes of other potential γ subunits identified by their homology to the stargazin gene, CACNG7 is a five-, and not four-exon gene whose mRNA encodes a protein we have designated γ7. Expression of human γ7 has been localized specifically to brain. N-type current through CaV2.2 Channels was almost abolished when co-expressed transiently with γ7 in either Xenopus oocytes or COS-7 cells. Furthermore, immunocytochemistry and western blots show that γ7 has this effect by causing a large reduction in Expression of CaV2.2 rather than by interfering with trafficking or biophysical properties of the Channel. No effect of transiently expressed γ7 was observed on pre-existing endogenous N-type Calcium Channels in sympathetic neurones. Low homology to the stargazin-like γ subunits, different gene structure and the unique functional properties of γ7 imply that it represents a distinct subdivision of the family of proteins identified by their structural and sequence homology to stargazin.
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the novel product of a five exon stargazin related gene abolishes cav2 2 Calcium Channel Expression
The EMBO Journal, 2002Co-Authors: Fraser J. Moss, Patricia Viard, Anthony Davies, Federica Bertaso, Karen M. Page, Alex Graham, C Canti, Mary Plumpton, Christopher Plumpton, Jeffrey J. ClareAbstract:We have cloned and characterized a new member of the voltage-dependent Ca2+ Channel γ subunit family, with a novel gene structure and striking properties. Unlike the genes of other potential γ subunits identified by their homology to the stargazin gene, CACNG7 is a five-, and not four-exon gene whose mRNA encodes a protein we have designated γ7. Expression of human γ7 has been localized specifically to brain. N-type current through CaV2.2 Channels was almost abolished when co-expressed transiently with γ7 in either Xenopus oocytes or COS-7 cells. Furthermore, immunocytochemistry and western blots show that γ7 has this effect by causing a large reduction in Expression of CaV2.2 rather than by interfering with trafficking or biophysical properties of the Channel. No effect of transiently expressed γ7 was observed on pre-existing endogenous N-type Calcium Channels in sympathetic neurones. Low homology to the stargazin-like γ subunits, different gene structure and the unique functional properties of γ7 imply that it represents a distinct subdivision of the family of proteins identified by their structural and sequence homology to stargazin.
Karolina M. Turczyńska - One of the best experts on this subject based on the ideXlab platform.
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Regulation of vascular smooth muscle mechanotransduction by microRNAs and L-type Calcium Channels.
Communicative & integrative biology, 2013Co-Authors: Karolina M. Turczyńska, Karl Swärd, Per Hellstrand, Sebastian AlbinssonAbstract:The phenotype of smooth muscle cells is regulated by multiple environmental factors including mechanical forces. Mechanical stretch of mouse portal veins ex vivo has been shown to promote contractile differentiation by activation of the Rho-pathway, an effect that is dependent on the influx of Calcium via L-type Calcium Channels. MicroRNAs have recently been demonstrated to play a significant role in the control of smooth muscle phenotype and in a recent report we investigated their role in vascular mechanosensing. By smooth muscle specific deletion of Dicer, we found that microRNAs are essential for smooth muscle differentiation in response to stretch by regulating CamKIIδ and L-type Calcium Channel Expression. Furthermore, we suggest that loss of L-type Calcium Channels in Dicer KO is due to reduced Expression of the smooth muscle-enriched microRNA, miR-145, which targets CamKIIδ. These results unveil a novel mechanism for miR-145 dependent regulation of smooth muscle phenotype.
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MicroRNAs are essential for stretch-induced vascular smooth muscle contractile differentiation via miR-145-dependent Expression of L-type Calcium Channels
The Journal of biological chemistry, 2012Co-Authors: Karolina M. Turczyńska, Karl Swärd, Per Hellstrand, Mardjaneh Karbalaei Sadegh, Sebastian AlbinssonAbstract:Abstract Stretch of the vascular wall is an important stimulus to maintain smooth muscle contractile differentiation that is known to depend on L-type Calcium influx, Rho-activation, and actin polymerization. The role of microRNAs in this response was investigated using tamoxifen-inducible and smooth muscle-specific Dicer KO mice. In the absence of Dicer, which is required for microRNA maturation, smooth muscle microRNAs were completely ablated. Stretch-induced contractile differentiation and Rho-dependent cofilin-2 phosphorylation were dramatically reduced in Dicer KO vessels. On the other hand, acute stretch-sensitive growth signaling, which is independent of influx through L-type Calcium Channels, was not affected by Dicer KO. Contractile differentiation induced by the actin polymerizing agent jasplakinolide was not altered by deletion of Dicer, suggesting an effect upstream of actin polymerization. Basal and stretch-induced L-type Calcium Channel Expressions were both decreased in Dicer KO portal veins, and inhibition of L-type Channels in control vessels mimicked the effects of Dicer deletion. Furthermore, inhibition of miR-145, a highly expressed microRNA in smooth muscle, resulted in a similar reduction of L-type Calcium Channel Expression. This was abolished by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN93, suggesting that Ca2+/calmodulin-dependent protein kinase IIδ, a target of miR-145 and up-regulated in Dicer KO, plays a role in the regulation of L-type Channel Expression. These results show that microRNAs play a crucial role in stretch-induced contractile differentiation in the vascular wall in part via miR-145-dependent regulation of L-type Calcium Channels.