No evidence for altered intracellular calcium-handling in airway smooth muscle cells from human subjects with asthma.
BMC Pulm Med
; 15: 12, 2015 Feb 13.
Article
en En
| MEDLINE
| ID: mdl-25880173
ABSTRACT
BACKGROUND:
Asthma is characterized by airway hyper-responsiveness and variable airflow obstruction, in part as a consequence of hyper-contractile airway smooth muscle, which persists in primary cell culture. One potential mechanism for this hyper-contractility is abnormal intracellular Ca(2+) handling.METHODS:
We sought to compare intracellular Ca(2+) handling in airway smooth muscle cells from subjects with asthma compared to non-asthmatic controls by measuring i) bradykinin-stimulated changes in inositol 1,4,5-trisphosphate (IP3) accumulation and intracellular Ca(2+) concentration, ii) sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) expression, iii) mechanisms of cytoplasmic Ca(2+) clearance assessed following instantaneous flash photolytic release of Ca(2+) into the cytoplasm.RESULTS:
We found no differences in airway smooth muscle cell basal intracellular Ca(2+) concentrations, bradykinin-stimulated IP3 accumulation or intracellular Ca(2+) responses. Quantification of SERCA2 mRNA or protein expression levels revealed no differences in ASM cells obtained from subjects with asthma compared to non-asthmatic controls. We did not identify differences in intracellular calcium kinetics assessed by flash photolysis and calcium uncaging independent of agonist-activation with or without SERCA inhibition. However, we did observe some correlations in subjects with asthma between lung function and the different cellular measurements of intracellular Ca(2+) handling, with poorer lung function related to increased rate of recovery following flash photolytic elevation of cytoplasmic Ca(2+) concentration.CONCLUSIONS:
Taken together, the experimental results reported in this study do not demonstrate major fundamental differences in Ca(2+) handling between airway smooth muscle cells from non-asthmatic and asthmatic subjects. Therefore, increased contraction of airway smooth muscle cells derived from asthmatic subjects cannot be fully explained by altered Ca(2+) homeostasis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Asma
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ARN Mensajero
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Calcio
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Miocitos del Músculo Liso
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ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico
Tipo de estudio:
Observational_studies
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Prognostic_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2015
Tipo del documento:
Article