α1-Syntrophin–deficient skeletal muscle exhibits hypertrophy and aberrant formation of neuromuscular junctions during regeneration

α1-Syntrophin is a member of the family of dystrophin-associated proteins; it has been shown to recruit neuronal nitric oxide synthase and the water channel aquaporin-4 to the sarcolemma by its PSD-95/SAP-90, Discs-large, ZO-1 homologous domain. To examine the role of α1-syntrophin in muscle regeneration, we injected cardiotoxin into the tibialis anterior muscles of α1-syntrophin–null (α1syn−/−) mice. After the treatment, α1syn−/− muscles displayed remarkable hypertrophy and extensive fiber splitting compared with wild-type regenerating muscles, although the untreated muscles of the mutant mice showed no gross histological change. In the hypertrophied muscles of the mutant mice, the level of insulin-like growth factor-1 transcripts was highly elevated. Interestingly, in an early stage of the regeneration process, α1syn−/− mice showed remarkably deranged neuromuscular junctions (NMJs), accompanied by impaired ability to exercise. The contractile forces were reduced in α1syn−/− regenerating muscles. Our results suggest that the lack of α1-syntrophin might be responsible in part for the muscle hypertrophy, abnormal synapse formation at NMJs, and reduced force generation during regeneration of dystrophin-deficient muscle, all of which are typically observed in the early stages of Duchenne muscular dystrophy patients

-4 Heart Asia Roles of ghrelin in left-ventricular remodelling after acute myocardial infarction

. Multivariate regression analysis showed that ghrelin on day 14 is a significant predictor of LV remodelling after AMI (b¼ +0.44, p¼0.001). Conclusion To our knowledge, this is the first report that shows a relation between circulating ghrelin after AMI and the progression of LV remodelling in the chronic phase. The elevation of ghrelin after AMI might be a compensatory mechanism to attenuate LV remodelling

Effects of dantrolene and its derivatives on Ca(2+) release from the sarcoplasmic reticulum of mouse skeletal muscle fibres

1. We analysed the effect of dantrolene (Dan) and five newly synthesized derivatives (GIFs) on Ca(2+) release from the sarcoplasmic reticulum (SR) of mouse skeletal muscle. 2. In intact muscles, GIF-0185 reduced the size of twitch contraction induced by electrical stimulation to the same extent as Dan. GIF-0082, an azido-functionalized Dan derivative, also inhibited twitch contraction, although the extent of inhibition was less than that of Dan and of GIF-0185. 3. In skinned fibres, Dan inhibited Ca(2+)-induced Ca(2+) release (CICR) under Mg(2+)-free conditions at room temperature. In contrast, GIF-0082 and GIF-0185 showed no inhibitory effect on CICR under the same conditions. 4. Dan-induced inhibition of CICR was not affected by the presence of GIF-0082, whereas it was diminished in the presence of GIF-0185. 5. GIF-0082 and GIF-0185 significantly inhibited clofibric acid (Clof)-induced Ca(2+) release, as did Dan. 6. Several Dan derivatives other than GIF-0082 and GIF-0185 showed an inhibitory effect on twitch tension but not on the CICR mechanism. All of these derivatives inhibited Clof-induced Ca(2+) release. 7. The magnitudes of inhibition of Clof-induced Ca(2+) release by all Dan derivatives were well correlated with those of twitch inhibition. This supports the notion that the mode of Clof-induced opening of the RyR-Ca(2+) release channel may be similar to that of physiological Ca(2+) release (PCR). 8. These results indicate that the difference in opening modes of the RyR-Ca(2+) release channel is recognized by certain Dan derivatives