On a novel rate theory for transport in narrow ion channels and its application to the study of flux optimization via geometric effects
We present a novel rate theory based on the notions of splitting probability and mean first passage time to describe single-ion conduction in narrow, effectively one-dimensional membrane channels. In contrast to traditional approaches such as transition state theory or Kramers theory, transitions be...
Saved in:
Published in | The Journal of chemical physics Vol. 130; no. 8; p. 085101 |
---|---|
Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
28.02.2009
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Abstract | We present a novel rate theory based on the notions of splitting probability and mean first passage time to describe single-ion conduction in narrow, effectively one-dimensional membrane channels. In contrast to traditional approaches such as transition state theory or Kramers theory, transitions between different conduction states in our model are governed by rates which depend on the full geometry of the potential of mean force (PMF) resulting from the superposition of an equilibrium free energy profile and a transmembrane potential induced by a nonequilibrium constraint. If a detailed theoretical PMF is available (e.g., from atomistic molecular dynamics simulations), it can be used to compute characteristic conductance curves in the framework of our model, thereby bridging the gap between the atomistic and the mesoscopic level of description. Explicit analytic solutions for the rates, the ion flux, and the associated electric current can be obtained by approximating the actual PMF by a piecewise linear potential. As illustrative examples, we consider both a theoretical and an experimental application of the model. The theoretical example is based on a hypothetical channel with a fully symmetric sawtooth equilibrium PMF. For this system, we explore how changes in the spatial extent of the binding sites affect the rate of transport when a linear voltage ramp is applied. Already for the case of a single binding site, we find that there is an optimum size of the site which maximizes the current through the channel provided that the applied voltage exceeds a threshold value given by the binding energy of the site. The above optimization effect is shown to arise from the complex interplay between the channel structure and the applied electric field, expressed by a nonlinear dependence of the rates with respect to the linear size of the binding site. In studying the properties of current-voltage curves, we find a double crossover between sublinear and superlinear behaviors as the size of the binding site is varied. The ratio of unidirectional fluxes clearly deviates from the Ussing limit and can be characterized by a flux ratio exponent which decreases below unity as the binding site becomes wider. We also explore effects arising from changes in the ion bulk concentration under symmetric ionic conditions and the presence of additional binding sites in the hypothetical channel. As for the experimental application, we show that our rate theory is able to provide good fits to conductance data for sodium permeation through the gramicidin A channel. Possible extensions of the theory to treat the case of an asymmetric equilibrium PMF, fluctuations in the mean number of translocating ions, the case of fluctuating energy barriers, and multi-ion conductance are briefly discussed. |
---|---|
AbstractList | We present a novel rate theory based on the notions of splitting probability and mean first passage time to describe single-ion conduction in narrow, effectively one-dimensional membrane channels. In contrast to traditional approaches such as transition state theory or Kramers theory, transitions between different conduction states in our model are governed by rates which depend on the full geometry of the potential of mean force (PMF) resulting from the superposition of an equilibrium free energy profile and a transmembrane potential induced by a nonequilibrium constraint. If a detailed theoretical PMF is available (e.g., from atomistic molecular dynamics simulations), it can be used to compute characteristic conductance curves in the framework of our model, thereby bridging the gap between the atomistic and the mesoscopic level of description. Explicit analytic solutions for the rates, the ion flux, and the associated electric current can be obtained by approximating the actual PMF by a piecewise linear potential. As illustrative examples, we consider both a theoretical and an experimental application of the model. The theoretical example is based on a hypothetical channel with a fully symmetric sawtooth equilibrium PMF. For this system, we explore how changes in the spatial extent of the binding sites affect the rate of transport when a linear voltage ramp is applied. Already for the case of a single binding site, we find that there is an optimum size of the site which maximizes the current through the channel provided that the applied voltage exceeds a threshold value given by the binding energy of the site. The above optimization effect is shown to arise from the complex interplay between the channel structure and the applied electric field, expressed by a nonlinear dependence of the rates with respect to the linear size of the binding site. In studying the properties of current-voltage curves, we find a double crossover between sublinear and superlinear behaviors as the size of the binding site is varied. The ratio of unidirectional fluxes clearly deviates from the Ussing limit and can be characterized by a flux ratio exponent which decreases below unity as the binding site becomes wider. We also explore effects arising from changes in the ion bulk concentration under symmetric ionic conditions and the presence of additional binding sites in the hypothetical channel. As for the experimental application, we show that our rate theory is able to provide good fits to conductance data for sodium permeation through the gramicidin A channel. Possible extensions of the theory to treat the case of an asymmetric equilibrium PMF, fluctuations in the mean number of translocating ions, the case of fluctuating energy barriers, and multi-ion conductance are briefly discussed. |
Author | Sansom, M S P Abad, E Reingruber, J |
Author_xml | – sequence: 1 givenname: E surname: Abad fullname: Abad, E email: enrique.abad@bioch.ox.ac.uk organization: Department of Biochemistry, Structural Bioinformatics and Computational Biochemistry Unit, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom. enrique.abad@bioch.ox.ac.uk – sequence: 2 givenname: J surname: Reingruber fullname: Reingruber, J – sequence: 3 givenname: M S P surname: Sansom fullname: Sansom, M S P |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19256626$$D View this record in MEDLINE/PubMed |
BookMark | eNo1kEtOwzAURS0Eoh8YsAH0NpDybCdOMkQVP6lSJzCu7MSmRokd2W4hbIBt06owOoN7dQZnRs6dd5qQG4oLioLf0QXHsmRYnJEpxarOSlHjhMxi_EBEWrL8kkxozQohmJiSn7UDCc7vdQdBJg1pq30YwfgAKUgXBx8SWAdOhuA_wXoHzVY6p7sI0rVg04HD0NlGpuOY_FEBMe3aEbwB0-2-wA_J9vb79NhbCe_a9zoF24A2RjcpXpELI7uor_84J2-PD6_L52y1fnpZ3q-yhlU8ZaxW3Mict0Zxroxk2EhRYSMKzjRqValCMa2Q5kIcInDKSslLKoqWmgJzwebk9uQddqrX7WYItpdh3PwXYb9q7GOP |
CitedBy_id | crossref_primary_10_1021_acs_jpcc_6b00443 crossref_primary_10_1103_PhysRevE_97_062158 crossref_primary_10_1137_120882780 crossref_primary_10_1021_acs_jpcb_6b09638 crossref_primary_10_1063_1_3580562 crossref_primary_10_1088_1361_648X_aac972 crossref_primary_10_1103_PhysRevE_94_052127 crossref_primary_10_1039_c2nr31024d crossref_primary_10_1021_ct4005933 crossref_primary_10_1142_S0219477519400078 crossref_primary_10_1016_j_cplett_2017_12_041 crossref_primary_10_1063_1_4871694 |
ContentType | Journal Article |
DBID | CGR CUY CVF ECM EIF NPM |
DOI | 10.1063/1.3077205 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
Discipline | Chemistry Physics |
EISSN | 1089-7690 |
ExternalDocumentID | 19256626 |
Genre | Research Support, Non-U.S. Gov't Journal Article |
GrantInformation_xml | – fundername: Biotechnology and Biological Sciences Research Council grantid: B19456 – fundername: Biotechnology and Biological Sciences Research Council grantid: BEP17032 – fundername: Biotechnology and Biological Sciences Research Council grantid: BBS/B/16011 – fundername: Biotechnology and Biological Sciences Research Council grantid: BB/H000267/1 – fundername: Biotechnology and Biological Sciences Research Council |
GroupedDBID | --- -DZ -ET -~X 123 1UP 2-P 29K 4.4 53G 5VS 6TJ 85S AAAAW AABDS AAEUA AAPUP AAYIH ABPPZ ABRJW ABZEH ACBRY ACLYJ ACNCT ACZLF ADCTM AEJMO AENEX AFATG AFFNX AFHCQ AGKCL AGLKD AGMXG AGTJO AHSDT AJJCW AJQPL ALEPV ALMA_UNASSIGNED_HOLDINGS AQWKA ATXIE AWQPM BDMKI BPZLN CGR CS3 CUY CVF D-I DU5 EBS ECM EIF EJD ESX F5P FDOHQ FFFMQ HAM M6X M71 M73 MVM N9A NPM NPSNA O-B P0- P2P RIP RNS ROL RQS TN5 TWZ UPT UQL WH7 YQT YZZ ~02 |
ID | FETCH-LOGICAL-c283t-29b3fa43dfb33bfa20ca680c6532e0eb8b5b2eb014667203127a37165d1f50462 |
IngestDate | Sat Sep 28 07:56:10 EDT 2024 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 8 |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c283t-29b3fa43dfb33bfa20ca680c6532e0eb8b5b2eb014667203127a37165d1f50462 |
PMID | 19256626 |
ParticipantIDs | pubmed_primary_19256626 |
PublicationCentury | 2000 |
PublicationDate | 2009-02-28 |
PublicationDateYYYYMMDD | 2009-02-28 |
PublicationDate_xml | – month: 02 year: 2009 text: 2009-02-28 day: 28 |
PublicationDecade | 2000 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | The Journal of chemical physics |
PublicationTitleAlternate | J Chem Phys |
PublicationYear | 2009 |
SSID | ssj0001724 |
Score | 2.0511558 |
Snippet | We present a novel rate theory based on the notions of splitting probability and mean first passage time to describe single-ion conduction in narrow,... |
SourceID | pubmed |
SourceType | Index Database |
StartPage | 085101 |
SubjectTerms | Biological Transport Electrophysiology Ion Channels - metabolism Kinetics Membrane Potentials Models, Biological |
Title | On a novel rate theory for transport in narrow ion channels and its application to the study of flux optimization via geometric effects |
URI | https://www.ncbi.nlm.nih.gov/pubmed/19256626 |
Volume | 130 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Nb9QwELW2IASXCgoUyofmwC1KSRzHyR6rClQh0SJopd4q27FRpa5TQbaq-gc49i93nImzUfkQcImiWIk2fm_HL2O_MWNvcIjIjcts6qysU8G1SedGqFQ0gufKNlY0IaH_cV_uHYkPx-XxbHY9WbW07PS2ufqlr-R_UMVriGtwyf4DsuND8QKeI754RITx-FcYH_hEJb69sGdJqPhArkRagdnFouUhoeH7SotJQDoYfT2Oh-OkwWQGO-rQ77HQtDtbXiYtBpXF4NZMLk5V8tW2i7APl4mLQaYCd2U160WuifUIKIMyCvgdTdQafRCfLY6h35aaGLSaq8K3aClrm3wZvGgxRzGfeL4txdWsnqeVpJ1Bx8A7zMgQw-pJGA06kHIcP0V4lFQh2bCNsanivWO7myB9vuihRtmKMpWs-H9uvVVsOzatsbWqDgFzPyR_hoEdtZ6Ixalk8Xb8DX3hWbrv1sdJL1IOH7L1oeNhh6jyiM2s32D3d-Omfhvs3ifC4TH7ceBBQU8eCOQBIg8geWAkD5x6IPIAog-RPIDkASQPTMgDXRseAT15oHUQyANT8gCSB0bywECeJ-zo_bvD3b102JUjNShFu5TPdeGUKBqni0I7xTOjZJ0ZWRbcZlbXutTc6lCUSIY5_pxXqsCv8rLJXRms0E_ZHd96-4xBoZR2FSpaK6zQUilbutxInpvGoa6sn7NN6s2Tcyq9chL7eeu3LS_YgxUDX7K7Dv_r9hUKx06_7uG8Ad8sctk |
link.rule.ids | 786 |
linkProvider | National Library of Medicine |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=On+a+novel+rate+theory+for+transport+in+narrow+ion+channels+and+its+application+to+the+study+of+flux+optimization+via+geometric+effects&rft.jtitle=The+Journal+of+chemical+physics&rft.au=Abad%2C+E&rft.au=Reingruber%2C+J&rft.au=Sansom%2C+M+S+P&rft.date=2009-02-28&rft.eissn=1089-7690&rft.volume=130&rft.issue=8&rft.spage=085101&rft_id=info:doi/10.1063%2F1.3077205&rft_id=info%3Apmid%2F19256626&rft_id=info%3Apmid%2F19256626&rft.externalDocID=19256626 |