Synaptic Cleft Acidification and Modulation of Short-Term Depression by Exocytosed Protons in Retinal Bipolar Cells

Mary J. Palmer, Court Hull, Jozsef Vigh, Henrique Von Gersdorff

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


The release of vesicular protons during exocytosis causes a feedback inhibition of Ca2+ channels in photoreceptor terminals; however, the effect of this inhibition on subsequent exocytosis has not been studied. Here we show that a similar L-type Ca2+ channel inhibition occurs in bipolar cell terminals in slices of goldfish retina, and we investigate the effect that this has on subsequent exocytosis with membrane capacitance measurements. We find that transient Ca2+ current inhibition is correlated with exocytosis and modulated by the concentration of extracellular pH buffer. Ca2+ current inhibition is negligible in acutely dissociated terminals, demonstrating the importance of an intact synaptic cleft. The sensitivity of bipolar cell Ca2+ currents to extracellular pH was assessed: channel conductance is reduced and activation is shifted to more positive potentials by acidification. The effect of Ca2+ current inhibition on subsequent exocytosis was investigated by measuring paired-pulse depression. Under conditions in which there is a large amount of inhibition of Ca2+ influx, the degree of paired-pulse depression is significantly reduced. Finally, we show that under physiological (bicarbonate) buffering conditions, pronounced Ca2+ current inhibition occurs after exocytosis (∼60% peak inhibition), which can decrease subsequent exocytosis during single depolarizations. We estimate that exocytosis is accompanied by a transient change in synaptic cleft pH from 7.5 to ∼6.9. We suggest that this effect serves as an activity-dependent modulator of exocytosis at ribbon-type synapses where a large and compact coterie of vesicles can fuse at each active zone.

Original languageEnglish (US)
Pages (from-to)11332-11341
Number of pages10
JournalJournal of Neuroscience
Issue number36
StatePublished - Dec 10 2003


  • Bipolar cell
  • Exocytosis
  • Goldfish retina
  • Membrane capacitance
  • Paired-pulse depression
  • Presynaptic terminal
  • Synaptic ribbon
  • Vesicular pH

ASJC Scopus subject areas

  • Neuroscience(all)


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