Two independent pathways mediated by cAMP and protein kinase A enhance spontaneous transmitter release at Drosophila neuromuscular junctions.
JOURNAL OF NEUROSCIENCE(2000)
摘要
cAMP is thought to be involved in learning process and known to enhance transmitter release in various systems. Previously we reported that cAMP enhances spontaneous transmitter release in the absence of extracellular Ca2+ and that the synaptic vesicle protein neuronal-synaptobrevin (n-syb), is required in this enhancement (n-syb-dependent; Yoshihara et al., 1999). In the present study, we examined the cAMP-induced enhancement of transmitter release in the presence of external Ca2+. We raised the intracellular concentration of cAMP by application of either forskolin, an activator of adenylyl cyclase, or by 4-chlorophenylthio-(CPT) cAMP, a membrane-permeable analog of cAMP, in the presence of external Ca2+, while recording miniature synaptic currents (mSCs) at the neuromuscular junction in n-syb null mutant embryos. The frequency of mSCs increased in response to elevation of cAMP, and this effect of cAMP was completely blocked by Co2+ (n-syb-independent pathway). In contrast, in wild-type embryos the cAMP-induced mSC frequency increase was partially blocked by Co2+. In a mutant, DC0, defective in protein kinase A (PKA), nerve-evoked synaptic currents were indistinguishable from the control, but mSCs were less frequent. In this mutant the enhancement by cAMP of both nerve-evoked and spontaneous transmitter release was completely absent, even in the presence of external Ca2+. Taken together, these results suggest that cAMP enhances spontaneous transmitter release by increasing Ca2+ influx (n-syb-independent) as well as by modulating the release mechanism without Ca2+ influx (n-syb-dependent) in wild-type embryos, and these two effects are mediated by PKA encoded by the DC0 gene.
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关键词
cAMP,spontaneous synaptic currents,neuronal-synaptobrevin,DC0,PKA,forskolin,neuromuscular junction,Drosophila,myosin heavy chain mutant
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