Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca2+ channels via microdomain coupling

J Neurosci. 2012 Oct 10;32(41):14294-304. doi: 10.1523/JNEUROSCI.6104-11.2012.


The coupling between presynaptic Ca(2+) channels and Ca(2+) sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca(2+) channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic opening of presynaptic Ca(2+) channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca(2+) concentration and the unselective Ca(2+) channel blocker Cd(2+) reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ∼50%, suggesting that the opening of presynaptic Ca(2+) channels contributes to spontaneous release. Application of the selective P/Q-type Ca(2+) channel blocker ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced mIPSC frequency. Furthermore, both the fast Ca(2+) chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency, suggesting that Ca(2+)-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB(1) receptor agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca(2+)-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca(2+) channels may be important for hippocampal information processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels, L-Type / physiology*
  • Calcium Channels, N-Type / physiology*
  • Cytoplasmic Granules / chemistry
  • Cytoplasmic Granules / physiology*
  • Female
  • Hippocampus / physiology*
  • Inhibitory Postsynaptic Potentials / physiology*
  • Male
  • Membrane Microdomains / physiology*
  • Miniature Postsynaptic Potentials / physiology*
  • Organ Culture Techniques
  • Rats
  • Rats, Wistar


  • Calcium Channels, L-Type
  • Calcium Channels, N-Type