Phospholipase Cbeta serves as a coincidence detector through its Ca2+ dependency for triggering retrograde endocannabinoid signal.
Endocannabinoids mediate retrograde signal and modulate transmission efficacy at various central synapses. Although endocannabinoid release is induced by either depolarization or activation of G(q/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 Cbeta1 (PLCbeta1) in hippocampal neurons. By measuring cannabinoid-sensitive synaptic currents, we found that the receptor-driven endocannabinoid release was dependent on physiological levels of intracellular Ca(2+) concentration ([Ca(2+)](i)), and markedly enhanced by depolarization-induced [Ca(2+)](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 [Ca(2+)](i) dependence to that of endocannabinoid release. Neither endocannabinoid release nor PLC activation was induced by receptor activation in PLCbeta1 knockout mice. We therefore conclude that PLCbeta1 serves as a coincidence detector through its Ca(2+) dependency for endocannabinoid release in hippocampal neurons.
Hashimotodani
Yuki
Y
Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
Ohno-Shosaku
Takako
T
Tsubokawa
Hiroshi
H
Ogata
Hidenori
H
Emoto
Ken
K
Maejima
Takashi
T
Araishi
Kenji
K
Shin
Hee-Sup
HS
Kano
Masanobu
M
D000818:Animals; D015374:Biosensing Techniques; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D063388:Endocannabinoids; D006624:Hippocampus / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D054799:Phospholipase C beta; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D015220:Calcium Channels; D063385:Cannabinoid Receptor Modulators; D004075:Diglycerides; D063388:Endocannabinoids; D007527:Isoenzymes; D011976:Receptors, Muscarinic; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D002118:Calcium