Few CaV1.3 Channels Regulate the Exocytosis of a Synaptic Vesicle at the Hair Cell Ribbon Synapseстатья из журнала
Аннотация: Hearing relies on faithful sound coding at hair cell ribbon synapses, which use Ca 2+ -triggered glutamate release to signal with submillisecond precision. Here, we investigated stimulus–secretion coupling at mammalian inner hair cell (IHC) synapses to explore the mechanisms underlying this high temporal fidelity. Using nonstationary fluctuation analysis on Ca 2+ tail currents, we estimate that IHCs contain ∼1700 Ca 2+ channels, mainly of Ca V 1.3 type. We show by immunohistochemistry that the Ca V 1.3 Ca 2+ channels are localized preferentially at the ribbon-type active zones of IHCs. We argue that each active zone holds ∼80 Ca 2+ channels, of which probably <10 open simultaneously during physiological stimulation. We then manipulated the Ca 2+ current by primarily changing single-channel current or open-channel number. Effects on exocytosis of the readily releasable vesicle pool (RRP) were monitored by membrane capacitance recordings. Consistent with the high intrinsic Ca 2+ cooperativity of exocytosis, RRP exocytosis changed nonlinearly with the Ca 2+ current when varying the single-channel current. In contrast, the apparent Ca 2+ cooperativity of RRP exocytosis was close to unity when primarily manipulating the number of open channels. Our findings suggest a Ca 2+ channel–release site coupling in which few nearby Ca V 1.3 channels impose high nanodomain [Ca 2+ ] on release sites in IHCs during physiological stimulation. We postulate that the IHC ribbon synapse uses this Ca 2+ nanodomain control of exocytosis to signal with high temporal precision already at low sound intensities.
Год издания: 2005
Авторы: Andreas Brandt, Darina Khimich, Tobias Moser
Издательство: Society for Neuroscience
Источник: Journal of Neuroscience
Ключевые слова: Hearing, Cochlea, Tinnitus, Genetics, Neural dynamics and brain function, Ion Channels and Receptors
Другие ссылки: Journal of Neuroscience (PDF)
Journal of Neuroscience (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)
Journal of Neuroscience (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)
Открытый доступ: hybrid
Том: 25
Выпуск: 50
Страницы: 11577–11585