A rapid, nongenomic pathway facilitates the synaptic transmission induced by retinoic acid at the developing synapse

Jau Cheng Liou, Shih Yin Ho, Meng Ru Shen, Yi Ping Liao, Wen Tai Chiu, Kai Hsiang Kang

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


We have previously shown that retinoic acid (RA), a factor highly expressed in spinal cord, rapidly and specifically enhances the spontaneous acetylcholine release at developing neuromuscular synapses in Xenopus cell culture, using whole-cell patch-clamp recording. We have now further investigated the underlying mechanisms that are involved in RA-induced facilitation on the frequency of spontaneous synaptic currents (SSCs). Buffering the rise of intracellular Ca2+ with BAPTA-AM hampered the facilitation of SSC frequency induced by RA. The prompt RA-enhanced SSC frequency 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+ influx through voltage-activated Ca2+ channels are not required. Application of membrane-permeable inhibitors of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] or ryanodine receptors effectively blocked the increase of SSC frequency elicited by RA. Treating cells with either wortmannin or LY294002, two structurally different inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase) and with the phospholipase Cγ (PLCγ) inhibitor U73122, abolished RA-induced facilitation of synaptic transmission. Preincubation of the cultures with pharmacological inhibitors, either genistein, a broad-spectrum tyrosine kinase inhibitor, or PP2, which predominantly inhibits the Src family of nonreceptor tyrosine kinase, completely abolished RA-induced synaptic facilitation. Taken collectively, these results suggest that RA elicits Ca2+ release from Ins(1,4,5)P3 and/or ryanodine-sensitive intracellular Ca2+ stores of the presynaptic nerve terminal. This is done via PLC-γ/PI 3-kinase signaling cascades and Src tyrosine kinase activation, leading to an enhancement of spontaneous transmitter release.

Original languageEnglish
Pages (from-to)4721-4730
Number of pages10
JournalJournal of Cell Science
Issue number20
Publication statusPublished - 2005 Oct 15

All Science Journal Classification (ASJC) codes

  • Cell Biology

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