Avtor/Urednik		Marš, T; King, MP; Miranda, AF; Walker, WF; Miš, K; Grubič, Z
Naslov		Functional innervation of cultured human skeletal muscle proceeds by two modes with regard to agrin effects
Tip		članek
Vir		Neuroscience
Vol. in št.		Letnik 118
Leto izdaje		2003
Obseg		str. 87-97
Jezik		eng
Abstrakt		Nerve-derived agrin is a specific isoform of agrin that promotes clustering of nicotinic acetylcholine receptors (AChRs) and other components of the neuromuscular junction (NMJ). We investigated the effects of agrin on functional maturation of NMJs at the early stages of synaptogenesis in human muscle. Specifically, we assessed the importance of agrin for the differentiation of developing NMJs to the stage where they are able to transmit signals that result in contractions of myotubes. We utilized an in vitro model in which human myotubes are innervated by neurons extending from spinal cord explants of fetal rat. This model is suitable for functional studies because all muscle contractions are the result of neuromuscular transmission and can be quantitated. An anti-agrin antibody, Agr 33, was applied to cocultures during de novo NMJ formation. Quantitative analyses demonstrated that Agr 33 reduced the number of AChR clusters to 20% of and their long axes to 50% of control, yet still permitted early, NMJ-mediated, muscle contractions that are normally observed in 7-10 day old co-cultures. However, at later times of development, the same treatment completely prevented the increase in the number of contracting units as compared with untreated cocultures. It is concluded that there are two modes of functional maturation of NMJs with regard to agrin effects: one that is insensitive and the other that is sensitive to agrin blockade. Agrininsensitive mode is limited to the small population of NMJs that become functional at the earlier stages of functional innervation. However, most of the NMJs become contractioncompetent at the later stages of the innervation process. These NMJs become functional only if agrin action is uncompromised. This is the first characterization of the contribution of agrin to NMJ development on human muscle. (Abstract truncated at 2000 characters).
Deskriptorji		MUSCLE, SKELETAL NEUROMUSCULAR JUNCTION MOTOR ENDPLATE AGRIN RECEPTORS, CHOLINERGIC COCULTURE SPINAL CORD ANTIBODIES, MONOCLONAL