Recovery of Electrogenesis in Skeletal Muscles after Cell Therapy of Myodystrophy in MDX Mice

摘要

Maintaining the necessary levels of the resting membrane potential (RMP) in skeletal muscles is obligatory for successful functioning of the neuromuscular system. A reduction of RMP leads to inactiva-tion of sodium channels, decrease in excitability,reduction of the duration and speed of the conduction of action potential, as well as to disorders in excitation-contraction coupling [1,2]. The consequences of the disorders in the electrogenesis are the most considerable in the postsynaptic region of the muscle membrane, where the potential of the endplate transforms into a propagating action potential. Inactivation of sodium channels in this region of the membrane leads to an increase in the threshold of generation of the muscle action potential and,consequently, to a decrease in the safety factor of the neuromuscular transmission [ 1 ]. It is well known that the RMPs in the postsynaptic region of intact mammalian skeletal muscle fibers are 2 to 4 mV higher than that outside of the synaptic region.This local hyperpolarization is due to an increase in the electrogenic activity of Na~+,K~+-ATPase because of its activation by acetylcholine released from motor nerve endings in a non-quantal form [3]. The local hyperpolarization is regarded as an important mechanism of structural and functional organization of the neuromuscular synapse [3, 4], in particular, as a factor preventing inactivation of sodium channels in the area of the membrane during prolonged intense quantal release of a neurotransmitter [5]. According to some data, the effect of non-quantal form of acetylcholine may be based on the functional and molecular interaction of nicotinic cholinoreceptor with Na~+,K~+-ATPase [5, 6].