TY - JOUR
T1 - Phospholipase Cβ serves as a coincidence detector through its Ca 2+ dependency for triggering retrograde endocannabinoid signal
AU - Hashimotodani, Yuki
AU - Ohno-Shosaku, Takako
AU - Tsubokawa, Hiroshi
AU - Ogata, Hidenori
AU - Emoto, Ken
AU - Maejima, Takashi
AU - Araishi, Kenji
AU - Shin, Hee Sup
AU - Kano, Masanobu
N1 - Funding Information:
We thank Y. Mori for a generous gift of mouse TRPC6 cDNA; T. Tabata for valuable comments on the manuscript; T. Kubota for helpful advice about making various pCa solutions; and Y. Fukudome, K. Sakamoto, and T. Mitani for their valuable help in some experiments. This work was supported by Grants-in Aid for Scientific Research (T.O.-S., H.T., and M.K.) and Special Coordination Funds for Promoting Science and Technology (M.K.) from the Ministry of Education, Science, Sports, Culture and Technology of Japan, and also by the Toyota Riken Foundation (M.K.) and the Cell Science Research Foundation (M.K.).
PY - 2005/1/20
Y1 - 2005/1/20
N2 - Endocannabinoids mediate retrograde signal and modulate transmission efficacy at various central synapses. Although endocannabinoid release is induced by either depolarization or activation of Gq/11-coupled receptors, it is markedly enhanced by the coincidence of depolarization and receptor activation. Here we report that this coincidence is detected by phospholipase Cβ1 (PLCβ1) in hippocampal neurons. By measuring cannabinoid-sensitive synaptic currents, we found that the receptor-driven endocannabinoid release was dependent on physiological levels of intracellular Ca2+ concentration ([Ca2+]i), and markedly enhanced by depolarization-induced [Ca2+]i elevation. Furthermore, we measured PLC activity in intact neurons by using exogenous TRPC6 channel as a biosensor for the PLC product diacylglycerol and found that the receptor-driven PLC activation exhibited similar [Ca2+]i dependence to that of endocannabinoid release. Neither endocannabinoid release nor PLC activation was induced by receptor activation in PLCβ1 knockout mice. We therefore conclude that PLCβ1 serves as a coincidence detector through its Ca2+ dependency for endocannabinoid release in hippocampal neurons.
AB - Endocannabinoids mediate retrograde signal and modulate transmission efficacy at various central synapses. Although endocannabinoid release is induced by either depolarization or activation of Gq/11-coupled receptors, it is markedly enhanced by the coincidence of depolarization and receptor activation. Here we report that this coincidence is detected by phospholipase Cβ1 (PLCβ1) in hippocampal neurons. By measuring cannabinoid-sensitive synaptic currents, we found that the receptor-driven endocannabinoid release was dependent on physiological levels of intracellular Ca2+ concentration ([Ca2+]i), and markedly enhanced by depolarization-induced [Ca2+]i elevation. Furthermore, we measured PLC activity in intact neurons by using exogenous TRPC6 channel as a biosensor for the PLC product diacylglycerol and found that the receptor-driven PLC activation exhibited similar [Ca2+]i dependence to that of endocannabinoid release. Neither endocannabinoid release nor PLC activation was induced by receptor activation in PLCβ1 knockout mice. We therefore conclude that PLCβ1 serves as a coincidence detector through its Ca2+ dependency for endocannabinoid release in hippocampal neurons.
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U2 - 10.1016/j.neuron.2005.01.004
DO - 10.1016/j.neuron.2005.01.004
M3 - Article
C2 - 15664177
AN - SCOPUS:12344311450
SN - 0896-6273
VL - 45
SP - 257
EP - 268
JO - Neuron
JF - Neuron
IS - 2
ER -