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Cell Calcium. 2009 Jul;46(1):30-8. doi: 10.1016/j.ceca.2009.03.018. Epub 2009 May 2.

Homeostatic and stimulus-induced coupling of the L-type Ca2+ channel to the ryanodine receptor in the hippocampal neuron in slices.

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Department of Biological Sciences, The University of Texas at Brownsville, 80 Fort Brown, Brownsville, TX 78520, USA.


Activity-dependent increase in cytosolic calcium ([Ca(2+)](i)) is a prerequisite for many neuronal functions. We previously reported a strong direct depolarization, independent of glutamate receptors, effectively caused a release of Ca(2+) from ryanodine-sensitive stores and induced the synthesis of endogenous cannabinoids (eCBs) and eCB-mediated responses. However, the cellular mechanism that initiated the depolarization-induced Ca(2+)-release is not completely understood. In the present study, we optically recorded [Ca(2+)](i) from CA1 pyramidal neurons in the hippocampal slice and directly monitored miniature Ca(2+) activities and depolarization-induced Ca(2+) signals in order to determine the source(s) and properties of [Ca(2+)](i)-dynamics that could lead to a release of Ca(2+) from the ryanodine receptor. In the absence of depolarizing stimuli, spontaneously occurring miniature Ca(2+) events were detected from a group of hippocampal neurons. This miniature Ca(2+) event persisted in the nominal Ca(2+)-containing artificial cerebrospinal fluid (ACSF), and increased in frequency in response to the bath-application of caffeine and KCl. In contrast, nimodipine, the antagonist of the L-type Ca(2+) channel (LTCC), a high concentration of ryanodine, the antagonist of the ryanodine receptor (RyR), and thapsigargin (TG) reduced the occurrence of the miniature Ca(2+) events. When a brief puff-application of KCl was given locally to the soma of individual neurons in the presence of glutamate receptor antagonists, these neurons generated a transient increase in the [Ca(2+)](i) in the dendrosomal region. This [Ca(2+)](i)-transient was sensitive to nimodipine, TG, and ryanodine suggesting that the [Ca(2+)](i)-transient was caused primarily by the LTCC-mediated Ca(2+)-influx and a release of Ca(2+) from RyR. We observed little contribution from N- or P/Q-type Ca(2+) channels. The coupling between LTCC and RyR was direct and independent of synaptic activities. Immunohistochemical study revealed a cellular localization of LTCC and RyR in a juxtaposed configuration in the proximal dendrites and soma. We conclude in the hippocampal CA1 neuron that: (1) homeostatic fluctuation of the resting membrane potential may be sufficient to initiate functional coupling between LTCC and RyR; (2) the juxtaposed localization of LTCC and RyR has anatomical advantage of synchronizing a Ca(2+)-release from RyR upon the opening of LTCC; and (3) the synchronized Ca(2+)-release from RyR occurs immediately after the activation of LTCC and determines the peak amplitude of depolarization-induced global increase in dendrosomal [Ca(2+)](i).

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