Ryanodine receptor regulates endogenous cannabinoid mobilization in the hippocampus.
نویسندگان
چکیده
Endogenous cannabinoids (eCBs) are produced and mobilized in a cytosolic calcium ([Ca2+]i)-dependent manner, and they regulate excitatory and inhibitory neurotransmitter release by acting as retrograde messengers. An indirect but real-time bioassay for this process on GABAergic transmission is DSI (depolarization-induced suppression of inhibition). The magnitude of DSI correlates linearly with depolarization-induced increase of [Ca2+]i that is thought to be initiated by Ca2+ influx through voltage-gated Ca2+ channels. However, the identity of Ca2+ sources involved in eCB mobilization in DSI remains undetermined. Here we show that, in CA1 pyramidal cells, DSI-inducing depolarizing voltage steps caused Ca2+-induced Ca2+ release (CICR) by activating the ryanodine receptor (RyR) Ca2+-release channel. CICR was reduced, and the remaining increase in [Ca2+]i was less effective in generating DSI, when the RyR antagonists, ryanodine or ruthenium red, were applied intracellularly, or the Ca2+ stores were depleted by the Ca2+-ATPase inhibitors, cyclopiazonic acid or thapsigargin. The CICR-dependent effects were most prominent in cultured or immature acute slices, but were also detectable in slices from adult tissue. Thus we suggest that voltage-gated Ca2+ entry raises local [Ca2+]i sufficiently to activate nearby RyRs and that the resulting CICR plays a critical role in initiating eCB mobilization. RyR may be a key molecule for the depolarization-induced production of eCBs that inhibit GABA release in the hippocampus.
منابع مشابه
The ryanodine receptor regulates endogenous cannabinoid mobilization in the hippocampus
Endogenous cannabinoids (eCBs) are produced and mobilized in a cytosolic calcium ([Ca]i) dependent manner, and they regulate excitatory and inhibitory neurotransmitter release by acting as retrograde messengers. An indirect but real time bioassay for this process on GABAergic transmission is DSI (depolarization-induced suppression of inhibition). The magnitude of DSI correlates linearly with de...
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ورودعنوان ژورنال:
- Journal of neurophysiology
دوره 95 5 شماره
صفحات -
تاریخ انتشار 2006