TY - JOUR
T1 - One-vesicle hypothesis for neurotransmitter release
T2 - A possible molecular mechanism
AU - Yusim, K.
AU - Parnas, H.
AU - Segel, L. A.
PY - 2001
Y1 - 2001
N2 - Neurotransmitter-containing vesicles are clustered in release sites. Although a given site can contain tens of vesicles, there is evidence that under a wide range of conditions, following an action potential, rarely is more than one vesicle released from each site. Such findings led to the one vesicle hypothesis, for which this paper suggests a molecular mechanism. The release of a vesicle from a site provides a transient high concentration of transmitter in that site. It is proposed here that the local high transmitter concentration interrupts further vesicle releases from the same release site. The suggested mechanism for this 'release interruption' is based on a theory of release control by the authors wherein inhibitory transmitter autoreceptors play a central role. (That transmitter binding to these autoreceptors can inhibit release on a fast time scale has recently been shown experimentally.) A detailed kinetic scheme is presented for the proposed mechanism. Stochastic simulations of this scheme demonstrate how the mechanism accounts for the one vesicle hypothesis. In agreement with recent experiments, the simulations also show that changes in conditions that affect the release process can cause frequent release of more than one vesicle per site.
AB - Neurotransmitter-containing vesicles are clustered in release sites. Although a given site can contain tens of vesicles, there is evidence that under a wide range of conditions, following an action potential, rarely is more than one vesicle released from each site. Such findings led to the one vesicle hypothesis, for which this paper suggests a molecular mechanism. The release of a vesicle from a site provides a transient high concentration of transmitter in that site. It is proposed here that the local high transmitter concentration interrupts further vesicle releases from the same release site. The suggested mechanism for this 'release interruption' is based on a theory of release control by the authors wherein inhibitory transmitter autoreceptors play a central role. (That transmitter binding to these autoreceptors can inhibit release on a fast time scale has recently been shown experimentally.) A detailed kinetic scheme is presented for the proposed mechanism. Stochastic simulations of this scheme demonstrate how the mechanism accounts for the one vesicle hypothesis. In agreement with recent experiments, the simulations also show that changes in conditions that affect the release process can cause frequent release of more than one vesicle per site.
UR - http://www.scopus.com/inward/record.url?scp=0035170920&partnerID=8YFLogxK
U2 - 10.1006/bulm.2001.0247
DO - 10.1006/bulm.2001.0247
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C2 - 11732174
AN - SCOPUS:0035170920
SN - 0092-8240
VL - 63
SP - 1025
EP - 1040
JO - Bulletin of Mathematical Biology
JF - Bulletin of Mathematical Biology
IS - 6
ER -