TY - JOUR
T1 - The chemical synapse goes electric
T2 - Ca2+- and voltage-sensitive GPCRs control neurotransmitter release
AU - Parnas, Hanna
AU - Parnas, Itzchack
PY - 2007/2
Y1 - 2007/2
N2 - It is widely believed that the initiation of transmitter release in fast synapses is triggered by rapid Ca2+ entry and that the termination of release is governed by removal of Ca2+ from below the release sites. We argue that, although Ca2+ is essential for release, fast-entry kinetics render Ca2+ incapable of being the limiting factor for the initiation of release, and the relatively slow removal of Ca2+ cannot be the limiting factor for the termination of release. We suggest, and provide supporting evidence for, a novel general mechanism for control of fast transmitter release (in the range of milliseconds) from nerve terminals. According to this mechanism, two factors control release: Ca2+ and voltage-sensitive presynaptic inhibitory G-protein-coupled receptors (GPCRs). Inhibitory autoreceptors are known to mediate slow feedback inhibition of transmitter release. We discuss the evidence showing that these receptors also control the initiation and termination of transmitter release by directly interacting with core proteins in the exocytotic machinery. This novel mechanism has important implications for understanding the regulation of transmitter release, synaptic plasticity and neuronal circuit properties.
AB - It is widely believed that the initiation of transmitter release in fast synapses is triggered by rapid Ca2+ entry and that the termination of release is governed by removal of Ca2+ from below the release sites. We argue that, although Ca2+ is essential for release, fast-entry kinetics render Ca2+ incapable of being the limiting factor for the initiation of release, and the relatively slow removal of Ca2+ cannot be the limiting factor for the termination of release. We suggest, and provide supporting evidence for, a novel general mechanism for control of fast transmitter release (in the range of milliseconds) from nerve terminals. According to this mechanism, two factors control release: Ca2+ and voltage-sensitive presynaptic inhibitory G-protein-coupled receptors (GPCRs). Inhibitory autoreceptors are known to mediate slow feedback inhibition of transmitter release. We discuss the evidence showing that these receptors also control the initiation and termination of transmitter release by directly interacting with core proteins in the exocytotic machinery. This novel mechanism has important implications for understanding the regulation of transmitter release, synaptic plasticity and neuronal circuit properties.
UR - http://www.scopus.com/inward/record.url?scp=33846502144&partnerID=8YFLogxK
U2 - 10.1016/j.tins.2006.12.001
DO - 10.1016/j.tins.2006.12.001
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.systematicreview???
C2 - 17169441
AN - SCOPUS:33846502144
SN - 0166-2236
VL - 30
SP - 54
EP - 61
JO - Trends in Neurosciences
JF - Trends in Neurosciences
IS - 2
ER -