The ryanodine receptor regulates endogenous cannabinoid mobilization in the hippocampus
نویسندگان
چکیده
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 depolarization-induced increase of [Ca]i that is thought to be initiated by Ca influx through voltage-gated Ca channels. However, the identity of Ca sources involved in eCB-mobilization in DSI remains undetermined. Here we show that, in CA1 pyramidal cells, DSI-inducing depolarizing voltage steps caused Ca induced Ca release (CICR) by activating the ryanodine receptor (RyR) Ca-release channel. CICR was reduced, and the remaining rise in [Ca]i was less effective in generating DSI, when the RyR antagonists, ryanodine or ruthenium red, were applied intracellularly, or the Ca stores were depleted by the Ca-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 Ca entry raises local [Ca]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
Ryanodine receptor regulates endogenous cannabinoid mobilization in the hippocampus.
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 ...
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