Developmental changes in Ca<sup>2+</sup> homeostasis and contractility in gallbladder smooth muscle

Camello-Almaraz, Cristina; Macias, Beatriz; Gomez‐Pinilla, Pedro J.; Alcon, Soledad Porte; Martín-Cano, Francisco E.; Baba, Akemishi; Matsuda, Takehisa; Camello, Pedro J.; Pozo, Marı́a J.

doi:10.1152/ajpcell.00452.2008

Cited by 16 publications

(12 citation statements)

References 41 publications

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“…Here, we show that aging displays opposite effects since it leads to an impairment of calcium sensitization pathways that is translated into hypocontractility of the gallbladder. These findings, together with results obtained in gallbladders from newborn guinea pigs (Camello-Almaraz et al 2009), draw the whole picture about the state of calcium sensitization along life. In guinea pig gallbladder, calcium sensitization pathway increases from birth to adult ages (CamelloAlmaraz et al 2009) and after that it suffers a decline.…”

Section: Discussionsupporting

confidence: 61%

Aging impairs Ca2+ sensitization pathways in gallbladder smooth muscle

Macias

Gomez‐Pinilla

Camello-Almaraz

et al. 2011

AGE

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Calcium sensitization is an important physiological process in agonist-induced contraction of smooth muscle. In brief, calcium sensitization is a pathway that leads to smooth muscle contraction independently of changes in [Ca 2+ ] i by mean of inhibition of myosin light chain phosphatase. Aging has negative impacts on gallbladder contractile response due to partial impairment in calcium signaling and alterations in the contractile machinery. However, information regarding aging-induced alterations in calcium sensitization is scanty. We hypothesized that the calcium sensitization system is negatively affected by age. To investigate this, gallbladders were collected from adult (4 months old) and aged (22-24 months old) guinea pigs. To evaluate the contribution of calcium sensitization pathways we assayed the effect of the specific inhibitors Y-27632 and GF109203X on the "in vitro" isometric gallbladder contractions induced by agonist challenges. In addition, expression and phosphorylation (as activation index) of proteins participating in the calcium sensitization pathways were quantified by Western blotting. Aging reduced bethanechol-and cholecystokinin-evoked contractions, an effect associated with a reduction in MLC20 phosphorylation and in the effects of both Y-27632 and GF109203X. In addition, there was a drop in ROCK I, ROCK II, MYPT-1 and PKC expression and in the activation/phosphorylation of MYPT-1, PKC and CPI-17 in response to agonists. Interestingly, melatonin treatment for 4 weeks restored gallbladder contractile responses due to re-establishment of calcium sensitization pathways. These results demonstrate that agerelated gallbladder hypocontractility is associated to alterations of calcium sensitization pathways and that melatonin treatment exerts beneficial effects in the recovery of gallbladder contractility.

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Section: Discussionsupporting

confidence: 61%

Aging impairs Ca2+ sensitization pathways in gallbladder smooth muscle

Macias

Gomez‐Pinilla

Camello-Almaraz

et al. 2011

AGE

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“…Consistent with previous studies with different neonatal SMs (8,9,11,12,14,31), we found that actin and myosin expression and specific active peak force elicited by KCl and carbachol at optimal length were lower compared with the adult. Specific force takes into account that the mechanical output depends on multiple factors, some of which are difficult to assess.…”

Section: Excitation Contraction Coupling In Relation To Contractile Psupporting

confidence: 92%

“…Although several studies addressed different aspects of the fetal and postnatal maturation of innervation, electrical activity, and global contractile activity of the GIT (5-7), only few studies addressed in some depth the properties of the downstream effector, the SM. Investigations from avian (8) and mammalian stomach (9)(10)(11), and guinea pig gallbladder (12) as well as from non-GIT organs like urinary bladder (13,14), revealed major differences between neonatal and adult tissues as regards electro-and pharmacomechanical coupling (14,15), protein composition, and functional properties of the contractile apparatus (14)(15)(16)(17). Interestingly, despite the widespread use of transgenic mouse models to investigate the contribution of individual proteins to the regulation of contraction (18)(19)(20), we are not aware of a systematic evaluation of biomechanics of the neonatal ileum coincident with its tissue architecture and protein composition of the contractile machinery.…”

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confidence: 99%

Neonatal mouse ileum: functional properties and protein composition of the contractile machinery

et al. 2014

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Background: Immature motility of the ileum may contribute to life-threatening diseases. Little is known about the normal biomechanics of the neonatal ileum in relation to the protein composition of its contractile machinery. Methods: We analyzed the tissue architecture, the biomechanics in intact and β-escin-permeabilized preparations, and the protein composition in neonatal (P0) and adult murine ileum. results: Muscle thickness of the P0 ileum was −50% of the adult ileum and passive compliance was higher. Carbachol-and KCl-elicited contractions were tonic rather than phasic as in the adult. Ca 2+ sensitivity was higher and relaxation rate was slower in β-escin-permeabilized P0 compared with adult ileum. The expression level of β-actin relative to α-actin was higher, and those of total actin, myosin, myosin light chain kinase, the catalytic subunit of myosin phosphatase and telokin were lower compared with the adult. The expression level of MYPT1 was similar, but P0 ileum expressed only the M133; the adult ileum also expressed the M130 isoform. conclusion: The mechanical features and protein composition of the P0 ileum are similar to those of adult tonic smooth muscles. We propose that this is highly adaptive during fetal life allowing the small intestine to act predominantly as a container. d uring development from fetal to newborn and adult life, the gastrointestinal tract (GIT) gradually establishes its mature structure and function. Anatomic features of the digestive tract are present already in human fetal life by 8 wk gestational age (1). However, gastrointestinal motility of preterm individuals is reduced (2). Obviously, this poses severe problems regarding oral food intake which are aggravated by the fact that the immaturity of the GIT, singly or in concert with other perinatal risk factors, may contribute to complications such as spontaneous intestinal perforation, not uncommon in extremely low-birth-weight infants (3). The underlying cause of spontaneous intestinal perforation, one of the leading risk factors of death in neonatal medicine, is still poorly understood. Conceivably an immature intestinal motility is an important determinant leading to stasis of the intestinal contents and overgrowth of infectious enteritis pathogens (4). The ensuing inflammatory response leads to a viscous cycle by not only further impairing of propulsive gut movements but also derogating vascular smooth muscle (SM) function, leading to reduced blood supply and finally to necrosis.Intestinal motility is driven by the concerted action of enteric neurons, pacemaker, and SM cells (2). Although several studies addressed different aspects of the fetal and postnatal maturation of innervation, electrical activity, and global contractile activity of the GIT (5-7), only few studies addressed in some depth the properties of the downstream effector, the SM. Investigations from avian (8) and mammalian stomach (9-11), and guinea pig gallbladder (12) as well as from non-GIT organs like urinary bladder (13,14), revealed major difference...

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“…Maturational differences in the calcium sensitization and desensitization pathways, as well as calcium handling, have been reported for other smooth muscle tissues, e.g., gallbladder (24). It has also been reported that ovine fetal cerebral arteries exhibit greater calcium sensitivity and http://physiolgenomics.physiology.org/ desensitization than do the mature arteries (89,148,186), though the mechanism has yet to be identified.…”

Section: Blood Vessel Developmentmentioning

confidence: 94%

Vascular smooth muscle phenotypic diversity and function

Fisher

2010

Physiological Genomics

145

141

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The control of force production in vascular smooth muscle is critical to the normal regulation of blood flow and pressure, and altered regulation is common to diseases such as hypertension, heart failure, and ischemia. A great deal has been learned about imbalances in vasoconstrictor and vasodilator signals, e.g., angiotensin, endothelin, norepinephrine, and nitric oxide, that regulate vascular tone in normal and disease contexts. In contrast there has been limited study of how the phenotypic state of the vascular smooth muscle cell may influence the contractile response to these signaling pathways dependent upon the developmental, tissue-specific (vascular bed) or disease context. Smooth, skeletal, and cardiac muscle lineages are traditionally classified into fast or slow sublineages based on rates of contraction and relaxation, recognizing that this simple dichotomy vastly underrepresents muscle phenotypic diversity. A great deal has been learned about developmental specification of the striated muscle sublineages and their phenotypic interconversions in the mature animal under the control of mechanical load, neural input, and hormones. In contrast there has been relatively limited study of smooth muscle contractile phenotypic diversity. This is surprising given the number of diseases in which smooth muscle contractile dysfunction plays a key role. This review focuses on smooth muscle contractile phenotypic diversity in the vascular system, how it is generated, and how it may determine vascular function in developmental and disease contexts.

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Developmental changes in Ca²⁺ homeostasis and contractility in gallbladder smooth muscle

Cited by 16 publications

References 41 publications

Aging impairs Ca2+ sensitization pathways in gallbladder smooth muscle

Aging impairs Ca2+ sensitization pathways in gallbladder smooth muscle

Neonatal mouse ileum: functional properties and protein composition of the contractile machinery

Vascular smooth muscle phenotypic diversity and function

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Developmental changes in Ca2+ homeostasis and contractility in gallbladder smooth muscle

Cited by 16 publications

References 41 publications

Aging impairs Ca2+ sensitization pathways in gallbladder smooth muscle

Aging impairs Ca2+ sensitization pathways in gallbladder smooth muscle

Neonatal mouse ileum: functional properties and protein composition of the contractile machinery

Vascular smooth muscle phenotypic diversity and function

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Developmental changes in Ca²⁺ homeostasis and contractility in gallbladder smooth muscle