Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca2+ channels via microdomain coupling.
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.
IST Austria (Institute of Science and Technology Austria), A-3400 Klosterneuburg, Austria.
Sarit Pati
SP
Goswami
Iancu
I
Bucurenciu
Peter
P
Jonas
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology*; D008297:Male; D021962:Membrane Microdomains / Q000502:physiology*; D055369:Miniature Postsynaptic Potentials / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar
D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type