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Developmental changes in Ca 2+ channel subtypes regulating endocytosis at the calyx of Held
Author(s) -
Midorikawa Mitsuharu,
Okamoto Yuji,
Sakaba Takeshi
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.273243
Subject(s) - endocytosis , calyx , microbiology and biotechnology , biology , chemistry , biophysics , neuroscience , genetics , anatomy , cell
Key points We examined the roles of each Ca 2+ channel subtype in the time course of endocytosis at the calyx of Held terminal by a capacitance measurement technique. At the calyx of Held terminal, endocytosis is mediated by two kinetically distinct components, a fast mode and a slow mode of endocytosis, in animals at postnatal days 8–11. R‐Type Ca 2+ channels are more tightly coupled to the slow mode of endocytosis than P/Q‐ and N‐type, demonstrating the differential contribution from different Ca 2+ channels to endocytosis. The fast mode of endocytosis, which was observed only following strong stimulation, was mainly mediated by P/Q‐type Ca 2+ channels. In animals at postnatal days 14–17, when fast endocytosis becomes less prominent, slow endocytosis was regulated by Ca 2+ influx through P/Q‐type Ca 2+ channels, indicating developmental changes in the functional coupling between Ca 2+ channel subtypes and endocytosis.Abstract At the mammalian central synapse, Ca 2+ influx through Ca 2+ channels triggers neurotransmitter release by exocytosis of synaptic vesicles, which fuse with the presynaptic membrane and are subsequently retrieved by endocytosis. At the calyx of Held terminal, P/Q‐type Ca 2+ channels mainly mediate exocytosis, while N‐ and R‐type channels have a minor role in young terminals (postnatal days 8–11). The role of each Ca 2+ channel subtype in endocytosis remains to be elucidated; therefore, we examined the role of each type of Ca 2+ channel in endocytosis, by using whole‐cell patch‐clamp recordings in conjunction with capacitance measurement techniques. We found that at the young calyx terminal, when R‐type Ca 2+ channels were blocked, the slow mode of endocytosis was further slowed, while blocking of either P/Q‐ or N‐type Ca 2+ channels had no major effect. In more mature terminals (postnatal days 14–17), the slow mode of endocytosis was mainly triggered by P/Q‐type Ca 2+ channels, suggesting developmental changes in the regulation of the slow mode of endocytosis by different Ca 2+ channel subtypes. In contrast, a fast mode of endocytosis was observed after strong stimulation in young terminals that was mediated mainly by P/Q‐type, but not R‐ or N‐type Ca 2+ channels. These results suggest that different types of Ca 2+ channels regulate the two different modes of endocytosis. The results may also suggest that exo‐ and endocytosis are regulated independently at different sites in young animals but are more tightly coupled in older animals, allowing more efficient synaptic vesicle cycling adapted for fast signalling.