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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Doctoral Student (Bonn) Mr. Michael Gurevich, Undergraduate Student Ms. Gloria Zheng, Ward Melville High School Ms. Noshin Khan, High School |
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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 2013 - Gloria Zheng named semi-finalist in INTEL Science Talent Search Competition
June 2012 - Gloria Zheng accepted as a Simons Summer Research
Program Fellow
June 2011 - Nidhi Mann accepted as a Simons Summer Research Program Fellow
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]
