Glycine release is potentiated by cAMP via EPAC2 and Ca21 stores in a retinal interneuron

Marc A. Meadows, Veeramuthu Balakrishnan, Xiaohan Wang, Henrique von Gersdorff

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Neuromodulation via the intracellular second messenger cAMP is ubiquitous at presynaptic nerve terminals. This modulation of synaptic transmission allows exocytosis to adapt to stimulus levels and reliably encode information. The AII amacrine cell (AII-AC) is a central hub for signal processing in the mammalian retina. The main apical dendrite of the AII-AC is connected to several lobular appendages that release glycine onto OFF cone bipolar cells and ganglion cells. However, the influence of cAMP on glycine release is not well understood. Using membrane capacitance measurements from mouse AII-ACs to directly measure exocytosis, we observe that intracellular dialysis of 1 mM cAMP enhances exocytosis without affecting the L-type Ca21 current. Responses to depolarizing pulses of various durations show that the size of the readily releasable pool of vesicles nearly doubles with cAMP, while paired-pulse depression experiments suggest that release probability does not change. Specific agonists and antagonists for exchange protein activated by cAMP 2 (EPAC2) revealed that the cAMP-induced enhancement of exocytosis requires EPAC2 activation. Furthermore, intact Ca21 stores were also necessary for the cAMP potentiation of exocytosis. Postsynaptic recordings from OFF cone bipolar cells showed that increasing cAMP with forskolin potentiated the frequency of glycinergic spontaneous IPSCs. We propose that cAMP elevations in the AII-AC lead to a robust enhancement of glycine release through an EPAC2 and Ca21 store signaling pathway. Our results thus contribute to a better understanding of how AII-AC crossover inhibitory circuits adapt to changes in ambient luminance.

Original languageEnglish (US)
Pages (from-to)9503-9520
Number of pages18
JournalJournal of Neuroscience
Issue number3
StatePublished - Nov 17 2021


  • AII amacrine cell
  • CAMP
  • Calcium store
  • EPAC
  • Exocytosis
  • Retina

ASJC Scopus subject areas

  • Neuroscience(all)


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