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Numerical reconstruction of the quantal event at nicotinic synapses

Wathey, John C. and Nass, Menasche M. and Lester, Henry A. (1979) Numerical reconstruction of the quantal event at nicotinic synapses. Biophysical Journal, 27 (1). pp. 145-164. ISSN 0006-3495. PMCID PMC1328553. https://resolver.caltech.edu/CaltechAUTHORS:20201005-113706172

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Abstract

To test our present quantitative knowledge of nicotinic transmission, we reconstruct the postsynaptic conductance change that results after a presynaptic nerve terminal liberates a quantum of acetylcholine (ACh) into the synaptic cleft. The theory assumes that ACh appears suddenly in the cleft and that is subsequent fate is determined by radial diffusion, by enzymatic hydrolysis, and by binding to receptors. Each receptor has one channel and two ACh binding sites; the channel opens when both sites are occupied and the rate-limiting step id the binding and dissociation of the second ACh molecule. The calculations reproduce the experimentally measured growth phase (200 microseconds), peak number of open channels (2,000), and exponential decay phase. The time constant of the decay phase exceeds the channel duration by approximately equal to 20%. The normal event is highly localized: at the peak, two-thirds of the open channels are within an area of 0.15 micrometer 2. This represents 75% of the available channels within this area. The model also simulates voltage and temperature dependence and effects of inactivating esterase and receptors. The calculations show that in the absence of esterase, transmitter is buffered by binding to receptors and the postsynaptic response can be potentiated.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/s0006-3495(79)85208-xDOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1328553/PubMed CentralArticle
ORCID:
AuthorORCID
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1979 The Biophysical Society. Published by Elsevier Under an Elsevier user license. Received for publication 30 November 1978 and in revised form 10 February 1979. We thank D. L. Armstrong, M. E. Krouse, T. L. Rosenberry, M. M. Salpeter, and R. E. Sheridan for helpful discussion. This work was supported by the Muscular Dystrophy Association of America (postdoctoral fellowship to M.M.N. and grant-in-aid) and by the U.S. National Institutes of Health (Research Career Development Award NS-272 to H.A.L. and grant NS-11756).
Funders:
Funding AgencyGrant Number
Muscular Dystrophy AssociationUNSPECIFIED
NIH Postdoctoral FellowshipNS-272
NIHNS-11756
Issue or Number:1
PubMed Central ID:PMC1328553
Record Number:CaltechAUTHORS:20201005-113706172
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201005-113706172
Official Citation:J.C. Wathey, M.M. Nass, H.A. Lester, Numerical reconstruction of the quantal event at nicotinic synapses, Biophysical Journal, Volume 27, Issue 1, 1979, Pages 145-164, ISSN 0006-3495, https://doi.org/10.1016/S0006-3495(79)85208-X.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105799
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:05 Oct 2020 19:38
Last Modified:05 Oct 2020 19:38

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