Enlarging the European Union

Abstract

To my family Acknowledgements: Several people have contributed to the completion of my thesis to whom I owe a great debt of gratitude. First of all, I would like to thank my supervisor Prof Dr. Thomas Straubhaar for his continuous and close assistance and all his useful and helpful remarks. I am also indebted to the following persons: Prof Dr. Thomas Rutherford for his repeated help with the programming language MPSGE as well as all those other members of the GAMS-users list who spent their precious time answering my questions, Dr.

A hydrophobic funnel governs monovalent cation selectivity in the ion channel TRPM5

“…Ion selectivity is usually linked to the presence of specific binding sites in the channels’ SF and inner pore ( Hille, 2001 ; Zhou et al, 2001 ), cooperativity between the permeation kinetics of multiple such binding sites ( Hille, 2001 ; Köpfer et al, 2014 ; Ives et al, 2023 ; Derebe et al, 2011 ), ion desolvation ( Noskov and Roux, 2007 ; Kopec et al, 2018 ), or size exclusion effects ( Hille, 2001 ; Dudev and Lim, 2014 ). Our simulations showed, however, that no high-affinity binding sites for cations exist within the pore of TRPM5, that only minor ion desolvation effects occur, and that size exclusion does not play a role in selectivity.…”

Alanine serine cysteine transporter (ASCT) substrate binding site properties probed with hydroxyhomoserine esters

“…For specificity experiments with EAAT1, EAAT2, EAAC1 and EAAT5, the internal solution contained 10 mM glutamate. Compounds were applied externally to HEK293 cells expressing cDNA of interest suspended from a current recording electrode in whole cell configuration mode, as described by Hille 13 through a rapid solution exchange device described previously. 12 Cells were immersed in external buffer bath used to dissolve the compounds.…”

Single‐molecule bioelectronics

“…Ion channel proteins are found in the cellular membranes of all organisms, and they are involved in a wide range of critical cellular processes 5 . In a historical context, single-ion-channel recordings 6 may be considered the first successful single-molecule bioelectronic recordings of any type, and they are central to modern physiology.…”

“…For detailed treatments of ion channels the reader is referred to numerous texts 5,6 and reviews 7–11 on these diverse molecules; here we simply wish to emphasize measurement considerations that make single channels electrically detectable. Several laboratory arrangements can facilitate recording ionic currents through single membrane proteins, including classical small-diameter glass pipettes 13 , microfabricated glass 14 and polymer 15 apertures, and scanning electrochemical microscopes (SECM) 16 .…”