{"title":"突触传递过程中扩散对受体结合的影响","authors":"Meyer B Jackson","doi":"10.1016/j.bpj.2024.07.038","DOIUrl":null,"url":null,"abstract":"<p><p>Despite the importance of speed in synaptic transmission, in many synapses, neurotransmitters bind to their receptors at rates that appear to be slower than the diffusion limit. This assessment is generally based on a comparison with the Smoluchowski limit rather than an independent experimental analysis. In many synapses, miniature excitatory postsynaptic currents (mEPSCs) are controlled by the interplay between binding to receptors and diffusion of the neurotransmitter out of the synaptic cleft. A model for mEPSCs that incorporates these features was used to evaluate published data showing that elevated viscosity increases mEPSC amplitude. With diffusion-limited binding, the model predicts that raising the viscosity will decrease the amplitude rather than increase it. Diffusion-independent binding predicts an increase that is larger than that observed. To explore the intermediate behavior between the diffusion-limited and diffusion-independent extremes, a general expression for intermolecular rates was used that depends on both collision frequency and intrinsic reactivity. This analysis yielded an estimate for collision frequency that is about an order of magnitude above the measured rate of association and an order of magnitude below the Smoluchowski limit.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427808/pdf/","citationCount":"0","resultStr":"{\"title\":\"The impact of diffusion on receptor binding during synaptic transmission.\",\"authors\":\"Meyer B Jackson\",\"doi\":\"10.1016/j.bpj.2024.07.038\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Despite the importance of speed in synaptic transmission, in many synapses, neurotransmitters bind to their receptors at rates that appear to be slower than the diffusion limit. This assessment is generally based on a comparison with the Smoluchowski limit rather than an independent experimental analysis. In many synapses, miniature excitatory postsynaptic currents (mEPSCs) are controlled by the interplay between binding to receptors and diffusion of the neurotransmitter out of the synaptic cleft. A model for mEPSCs that incorporates these features was used to evaluate published data showing that elevated viscosity increases mEPSC amplitude. With diffusion-limited binding, the model predicts that raising the viscosity will decrease the amplitude rather than increase it. Diffusion-independent binding predicts an increase that is larger than that observed. To explore the intermediate behavior between the diffusion-limited and diffusion-independent extremes, a general expression for intermolecular rates was used that depends on both collision frequency and intrinsic reactivity. This analysis yielded an estimate for collision frequency that is about an order of magnitude above the measured rate of association and an order of magnitude below the Smoluchowski limit.</p>\",\"PeriodicalId\":8922,\"journal\":{\"name\":\"Biophysical journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-09-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427808/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biophysical journal\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.bpj.2024.07.038\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOPHYSICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biophysical journal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.bpj.2024.07.038","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/31 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOPHYSICS","Score":null,"Total":0}
The impact of diffusion on receptor binding during synaptic transmission.
Despite the importance of speed in synaptic transmission, in many synapses, neurotransmitters bind to their receptors at rates that appear to be slower than the diffusion limit. This assessment is generally based on a comparison with the Smoluchowski limit rather than an independent experimental analysis. In many synapses, miniature excitatory postsynaptic currents (mEPSCs) are controlled by the interplay between binding to receptors and diffusion of the neurotransmitter out of the synaptic cleft. A model for mEPSCs that incorporates these features was used to evaluate published data showing that elevated viscosity increases mEPSC amplitude. With diffusion-limited binding, the model predicts that raising the viscosity will decrease the amplitude rather than increase it. Diffusion-independent binding predicts an increase that is larger than that observed. To explore the intermediate behavior between the diffusion-limited and diffusion-independent extremes, a general expression for intermolecular rates was used that depends on both collision frequency and intrinsic reactivity. This analysis yielded an estimate for collision frequency that is about an order of magnitude above the measured rate of association and an order of magnitude below the Smoluchowski limit.
期刊介绍:
BJ publishes original articles, letters, and perspectives on important problems in modern biophysics. The papers should be written so as to be of interest to a broad community of biophysicists. BJ welcomes experimental studies that employ quantitative physical approaches for the study of biological systems, including or spanning scales from molecule to whole organism. Experimental studies of a purely descriptive or phenomenological nature, with no theoretical or mechanistic underpinning, are not appropriate for publication in BJ. Theoretical studies should offer new insights into the understanding ofexperimental results or suggest new experimentally testable hypotheses. Articles reporting significant methodological or technological advances, which have potential to open new areas of biophysical investigation, are also suitable for publication in BJ. Papers describing improvements in accuracy or speed of existing methods or extra detail within methods described previously are not suitable for BJ.