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Potentiation of quantal secretion by insulin-like growth factor-1 at developing motoneurons in Xenopus cell culture

Jau-Cheng Liou, Fong-Zu Tsai and Shih-Yin Ho

Although evidence suggests that insulin-like growth factor (IGF) plays an important role in the development and growth of the nervous system, the effect of IGF-1 in the regulation of neurotransmitter release in the peripheral nervous system remains unknown. Here we show that acute application of IGF-1, a factor widely expressed in developing myocytes, dose-dependently enhances the spontaneous acetylcholine (ACh) secretion at developing neuromuscular synapses in Xenopus cell culture using whole-cell patch clamp recording. We studied the role of endogenously released IGF-1 by examining the effect of IGF-1 antibody on the frequency of spontaneous synaptic currents (SSCs) at high-activity synapses, and found SSC frequency was markedly reduced at these high-activity synapses. The IGF-1-induced synaptic potentiation was not abolished when Ca²⁺ was eliminated from the culture medium or there was bath-application of the pharmacological Ca²⁺ channel inhibitor Cd²⁺, indicating that Ca²⁺ influxes through voltage-activated Ca²⁺ channels are not required. Application of membrane-permeable inhibitors of inositol 1,4,5-trisphosphate (IP₃) or ryanodine receptors effectively occluded the increase of SSC frequency elicited by IGF-I. Treating cells with the phosphoinositide-3 kinase (PI3-K) inhibitors wortmannin or LY294002, and with phospholipase C (PLC) inhibitor U73122, but not the inhibitor of mitogen-activated protein (MAP) kinase PD98059, abolished IGF-1-induced synaptic potentiation. Taken collectively, these results suggest that endogenously released IGF-1 from myocytes elicits Ca²⁺ release from IP₃- and/or ryanodine-sensitive intracellular Ca²⁺ stores of the presynaptic nerve terminal. This is done via PI3-K and PLC signalling cascades, leading to an enhancement of spontaneous transmitter release.

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				Y.-P. Liao, S.-Y. Ho, and J.-C. Liou Non-genomic regulation of transmitter release by retinoic acid at developing motoneurons in Xenopus cell culture J. Cell Sci., June 15, 2004; 117(14): 2917 - 2924. [Abstract] [Full Text] [PDF]