Cyclic AMP inhibits neuromuscular junction maturation mediated by intracellular Ca2+

The neuromuscular junction (NMJ) is established through initial contact of motor neuron axon with a skeletal muscle cell and the subsequent synaptic maturation. Previous studies have shown that cyclic AMP (cAMP) enhanced spinal neurons' survival and growth but inhibited synaptogenesis. Here, we find that elevating intracellular cAMP level of presynaptic neurons prevented NMJs from maturation both physiologically and morphologically. Importantly, cytosolic Ca2+ is essential for the inhibitory effects of cAMP on NMJ maturation. We show that depletion of intracellular Ca2+ store, rather than extracellular Ca2+, abolished the cAMP-dependent inhibition of synaptic maturation. Taken together, we demonstrate that Ca2+ released from intracellular Ca2+ stores regulates neurotrophic actions on NMJ maturation.