Laboratoire PECSA - Physicochimie des Electrolytes, Colloïdes, et Sciences
Analytiques - UMR 7195 UPMC/CNRS/ESPCI
SEMINAIRE
Pr. Bob Eisenberg
Department of Molecular Biophysics and Physiology
Rush Medical College, Chicago
Ions in Channels
Lundi 4 mai 2009 à 14h30
A la bibliothèque du laboratoire PECSA
Université Pierre et Marie Curie
Bâtiment F/74 – 7ème étage – porte 754
4, place Jussieu – 75005 Paris
Jean-François DUFRECHE
Laboratoire PECSA
Case 51, Université P. et M. Curie, Bat F74, Pièce 757
4 Place Jussieu, 75252 PARIS CEDEX 05, FRANCE
E-mail : jean-francois.dufreche@upmc.fr
Tel: (33 1) 44 27 22 03
Fax:(33 1) 44 27 32 28
Ions in Channels
Bob Eisenberg
Department of Molecular Biophysics, Rush University Medical Center, Chicago, IL 60612
USA,
E–mail: beisenbe@rush.edu
Channels are proteins with a hole down their middle that control a wide range of
biological function because they control the flow of ions and thus electric charge in and out
of cells: channels produce the electrical properties of the nervous system; they control the
heart beat and muscle contraction; channels control secretion of hormones and urine. A
substantial fraction of drugs act on channels. Thousands of biologists study channels
every day, recording current voltage (IV) relations from single molecules in a variety of
solutions and concentrations. The genetic code and amino acid sequence for hundreds of
channels are known, and new three-dimensional structures are reported every few
months.
Ion channels are appealing objects for physical investigation because conformation
changes are not involved in channel function, once the channel is open. Ions move in a
structure that does not vary even by 0.1Å on the biological time scale of 105 sec. Open
channels are appealing objects for chemical study because they effectively select among
chemically similar ions, under unfavorable circumstances. Channels are appealing objects
for physical study because they contain an enormous density of charge, fixed, mobile, and
induced. Channels are lined with a large density of induced and fixed charge, say 4
charges in a length of 20 Å, diameter of 5 Å, with a nearby ionic atmosphere of 10M
concentration (typical biological solutions have ionic concentrations ~200 mM and water
‘concentrations’ ~55M; ions/molecules that control proteins and channels typically work at
~106 M concentration). Direct simulation of channel behavior is difficult if not impossible,
because ion transit takes 10 nsec; concentrations of 106 to 55M must be accurately
represented in the same calculation, and macroscopic electric fields and concentration
gradients produce substantial flows, making equilibrium analysis unhelpful.
Lower resolution theories are surprisingly successful in describing selectivity and IV
relations: mean field treatments do quite well if they include electric field, crowded charge,
and induced charge, although the proper treatment of correlated motions (e.g., plug flow of
molecules in a single file) is a challenge.
The future seems to require simulations to evaluate parameters and establish
bounds of validity for lower resolution theories. Simulations are more helpful if they are
calibrated in standard situations and thereby shown to deal reliably with crowded charge,
electrostatic fields, and induced charge away from equilibrium.