Professor Departments of Anesthesiology and Physiology & Biophysics University at Stony Brook School of Medicine Stony Brook, New York 11794-8480 phone: 631-444-3458 fax: 631-444-2907 e-mail: James.Dilger@stonybrook.edu |
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| Ms. Kathrin Groeneveld,
Doctoral Student (Bonn) Ms. Ana Santa Cruz, Doctoral Student (Stony Brook) Mr. Michael Gurevich, Undergraduate Student |
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| Former Lab Members Dr. Man Liu, Postdoctoral Associate Emerita Ms. Yuson Chong, Technician Emerita Ms. Claire Mettewie, Technician Emerita Ms. Ana Maria Vidal, Technician Emerita |
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January 2011 - Sarah Toledano named semi-finalist in INTEL Science Talent Search Competition
January 2010 - Georgios Mourdoukoutas named semi-finalist in INTEL Science Talent Search Competition
January 2009 - Michael Gurevich named semi-finalist in INTEL
Science Talent Search Competition
June 2008 - Deeptankar (Deep) Demazumder accepted to John's
Hopkins clinical cardiology training program
June 2008 - Amy Varghese accepted as a Simons Summer Reseearch
Program Fellow
January 2008 - Mandy Liu moves to University of Illinois, Chicago
August 2007 - Yuson Chong steps down to begin NYU Nursing School
May 25, 2006 - Lab awards at Departmental Research Evening:
March 10, 2006 - Claire Mettewie retires after 21 outstanding years
March 8, 2006 - Bonnie Lam and Lana Castor advance to LISEF
finals
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High time-resolution records showing inhibition of acetylcholine (ACh)-activated currents by 100 µM pentobarbital (PB). The trace labeled "Control" was obtained by applying ACh
in the absence of PB. From Dilger et al, 1997. |
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The activation of ligand-gated ion channels at a neuronal synapse can be mimickedin vitro by rapidly applying the ligand to a cell or patch and recording the current. We use a rapid perfusion system that can apply a substance to an outside-out patch within 0.1 ms.
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The traces on the left side of the figure were obtained by perfusing 100 µM acetylcholine (ACh) onto a patch containing 7 ACh receptor channels. Channel openings are downward transitions at this potential of -100 mV. The black and red traces are 2 single sweeps; the gray dots show currents from 38 other sweeps. The blue trace is the ensemble average of the 40 sweeps. The rectangular steps seen in the black and red traces arise from the random opening and closing of single ion channels. There is a great variation in the duration of the channel currents (rectangle width) but the amplitude of the currents (rectangle height) is quite uniform - giving rise to bands of points at uniformly spaced levels of current. The right side of the figure is an amplitude histogram
turned on its side (red dots) turned on its side generated
from the 40 sweeps. The uppermost peak corresponds to the
baseline current. The other peaks correspond to 1, 2, ...
and 7 open channels. The histogram was fit to an 8 peaked
gaussian function (blue line). |
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The ensemble average current (blue trace) exhibits a rapid rising phase (0.2 ms), a slow decay due to desensitization (30 ms) and a faster decay due to the closing of channels after removal of ACh (5 ms). We also calculated the ensemble variance of the 40 sweeps. A plot of the variance vs the average (blue diamonds) reveals information about the time-dependence of channel open proabability. Time proceeds clockwise around the curve. At the peak current (negative currents), the variance is relatively low. As the channels desensitize (current decreases towards zero), the variance initially rises and then falls. The point at which the variance is maximal corresponds to an open channel probability of 50%. The red curve is a
binomial function that should describe the data if there
are 7, identical, non-interacting channels with a single
channel current of -3.8 pA. |
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J.P. Dilger and Y. Liu.
Desensitization of acetylcholine receptors in BC3H-1 cells.
Pflügers Archiv 420: 479-485, 1992. [abstract]
Y. Liu, J.P. Dilger.
Decamethonium is a partial agonist at the nicotinic acetylcholine
receptor channel.
Synapse 13: 57-62, 1993. [abstract]
J.P Dilger, R.S. Brett and L. A. Lesko.
Effects of isoflurane on acetylcholine receptor channels: 1.
Single-channel currents.
Molecular Pharmacology41:127-133, 1992. [abstract]
Y. Liu and J.P. Dilger.
Application of the one- and two-dimensional Ising models to
studies of cooperativity between ion channels.
Biophysical Journal 64: 26-35, 1993. [abstract]
J.P Dilger, R.S. Brett and H.I. Mody.
The effects of isoflurane on acetylcholine receptor channels: 2.
Currents elicited by rapid perfusion of acetylcholine.
Molecular Pharmacology44:1056-1063, 1993. [abstract]
J.P. Dilger, A.M. Vidal, H.I. Mody and Y. Liu.
Evidence for direct actions of general anesthetics on an ion
channel protein: A new look at a unified mechanism of action.
Anesthesiology 81: 431-442, 1994. [abstract]
Y. Liu, J.P. Dilger
and A.M. Vidal.
Effects of alcohols and volatile anesthetics on the activation of
nicotinic acetylcholine receptor channels.
Molecular Pharmacology 45: 1235-1241, 1994. [abstract]
J.P. Dilger and A.M. Vidal.
Cooperative interactions between general anesthetics and QX-222
within the pore of the ACh receptor ion channel.
Molecular Pharmacology 46: 169-175, 1994. [abstract]
J.P. Dilger, Y. Liu
and A.M. Vidal.
Interactions of general anaesthetics with single acetylcholine
receptor channels.
European Journal of Anaesthesiology 12: 31-39, 1995. [abstract]
J.P.
Dilger, R. Boguslavsky, M. Barann,
T. Katz and A.M. Vidal.
Mechanisms of barbiturate inhibition of acetylcholine receptor
channels.
Journal of General Physiology 109:401-414, 1997. [abstract]
G.R. Manecke,
J.P. Dilger, L.J. Kutner and P.J.
Poppers.
Auscultation revisited: The waveform and spectral characteristics
of breath sounds during general anesthesia.
International Journal of Clinical Monitoring and Computing
14:231-240, 1997. [abstract]
M. Barann, I.
Wenningmann and J.P. Dilger.
Interactions of general anesthetics within the pore of an ion
channel.
Toxicology Letters 100-101: 155-161, 1998. [abstract]
M. Barann, J.P.
Dilger, H. Bönisch, M.
Göthert, A. Dybek, and B.W. Urban.
Inhibition of 5-HT3 receptors by propofol: Equilibrium
and kinetic measurements.
Neuropharmacology. 39:1064-1074, 2000. [PMID: 10727717] [abstract]
I. Wenningmann
and J.P. Dilger.
Die Kinetik der Inhibition nichtdepolarisierender
Muskelrelaxantien am nikotinergen Acetylcholinrezeptor.
Anasthesiol Intensivmed Notfallmed Schmerzther. 35:607-608,
2000 [PMID: 11050974] [German text]
J.P Dilger.
Basic Pharmacology of Volatile Anesthetics. In: Molecular Bases of
Anesthesia,
E. Moody and P. Skolnick, eds, CRC Press, Boca Raton, FL, 2001,
pp. 1-35. [book]
E.I. Eger, D.M.
Fisher, J.P. Dilger, J.M. Sonner,
A. Evers, N.P. Franks, R.A. Harris, J.J. Kendig, W.R. Leib and
T. Yamakura.
Relevant concentrations of inhaled anesthetics for in vitrostudies
of anesthetic mechanisms.
Anesthesiology 94:915-921, 2001. [PMID: 11388545] [abstract]
G. Spitzmaul,
J.P. Dilger and C. Bouzat.
The noncompetitive inhibitor quinacrine modifies the
desensitization kinetics of muscle acetylcholine receptors.
Molecular Pharmacology 60:235-243, 2001. [PMID: 11455009] [abstract]
[full
text] [pdf]
I. Wenningmann,
M. Barann, A.M. Vidal and J.P. Dilger.
The Effects of Isoflurane on Acetylcholine Receptor Channels: 3.
Effects of Conservative Polar-to-Nonpolar Mutations within the
Channel Pore.
Molecular Pharmacology 60: 584-594, 2001. [PMID: 11502891]
[abstract]
[full
text] [pdf]
I. Wenningmann
and J.P. Dilger.
The kinetics of inhibition of nicotinic acetylcholine receptors by
(+)-tubocurarine and pancuronium.
Molecular Pharmacology 60: 790-796, 2001. [PMID: 11562442]
[abstract]
[full
text] [pdf]
D. Demazumder
and J.P. Dilger.
The kinetics of competitive antagonism by cisatracurium of
embryonic and adult nicotinic acetylcholine receptors.
Molecular Pharmacology 60: 797-807, 2001. [PMID: 11562443]
[abstract]
[full
text] [pdf]
