Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published February 1996 | Published
Journal Article Open

A multi-substrate single-file model for ion-coupled transporters


Ion-coupled transporters are simulated by a model that differs from contemporary alternating-access schemes. Beginning with concepts derived from multi-ion pores, the model assumes that substrates (both inorganic ions and small organic molecules) hop a) between the solutions and binding sites and b) between binding sites within a single-file pore. No two substrates can simultaneously occupy the same site. Rate constants for hopping can be increased both a) when substrates in two sites attract each other into a vacant site between them and b) when substrates in adjacent sites repel each other. Hopping rate constants for charged substrates are also modified by the membrane field. For a three-site model, simulated annealing yields parameters to fit steady-state measurements of flux coupling, transport-associated currents, and charge movements for the GABA transporter GAT1. The model then accounts for some GAT1 kinetic data as well. The model also yields parameters that describe the available data for the rat 5-HT transporter and for the rabbit Na(+)-glucose transporter. The simulations show that coupled fluxes and other aspects of ion transport can be explained by a model that includes local substrate-substrate interactions but no explicit global conformational changes.

Additional Information

© 1996 The Biophysical Society; Published by Elsevier Inc. Received for publication 25 July 1995 and in final form 21 October 1995. Available online 2 January 2009. We thank Eric Bax, Bassil Dahiyat, Norman Davidson, and Jun Li for suggestions. Scott Fraser suggested the diffusion pump analogy. This work was supported by grants from the National Institute of Neurological Diseases and Stroke and the National Institute on Drug Abuse. SLM acknowledges support from the Rita Allen Foundation, the David and Lucille Packard Foundation, and the Searle Scholars Program.

Attached Files

Published - Su_1996_Biophys_J_A_multi-substrate_single-file_model_for.pdf


Files (2.2 MB)

Additional details

August 20, 2023
October 23, 2023