Alternative splicing alterations of Ca2+ handling genes are associated with Ca2+ signal dysregulation in myotonic dystrophy type 1 (DM1) and type 2 (DM2) myotubes.
Neuropathol Appl Neurobiol
; 40(4): 464-76, 2014 Jun.
Article
en En
| MEDLINE
| ID: mdl-23888875
ABSTRACT
AIMS:
The pathogenesis of myotonic dystrophy type 1 (DM1) and type 2 (DM2) has been related to the aberrant splicing of several genes, including those encoding for ryanodine receptor 1 (RYR1), sarcoplasmatic/endoplasmatic Ca(2+)-ATPase (SERCA) and α1S subunit of voltage-gated Ca(2+) channels (Cav 1.1). The aim of this study is to determine whether alterations of these genes are associated with changes in the regulation of intracellular Ca(2+) homeostasis and signalling.METHODS:
We analysed the expression of RYR1, SERCA and Cav 1.1 and the intracellular Ca(2+) handling in cultured myotubes isolated from DM1, DM2 and control muscle biopsies by semiquantitative RT-PCR and confocal Ca(2+) imaging respectively.RESULTS:
(i) The alternative splicing of RYR1, SERCA and Cav 1.1 was more severely affected in DM1 than in DM2 myotubes; (ii) DM1 myotubes exhibited higher resting intracellular Ca(2+) levels than DM2; (iii) the amplitude of intracellular Ca(2+) transients induced by sustained membrane depolarization was higher in DM1 myotubes than in controls, whereas DM2 showed opposite behaviour; and (iv) in both DM myotubes, Ca(2+) release from sarcoplasmic reticulum through RYR1 was lower than in controls.CONCLUSION:
The aberrant splicing of RYR1, SERCA1 and Cav 1.1 may alter intracellular Ca(2+) signalling in DM1 and DM2 myotubes. The differing dysregulation of intracellular Ca(2+) handling in DM1 and DM2 may explain their distinct sarcolemmal hyperexcitabilities.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Calcio
/
Empalme Alternativo
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Fibras Musculares Esqueléticas
/
Señalización del Calcio
/
Distrofia Miotónica
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
/
Aged
/
Humans
/
Middle aged
Idioma:
En
Revista:
Neuropathol Appl Neurobiol
Año:
2014
Tipo del documento:
Article
País de afiliación:
Italia