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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Student Mr. Fernando Barajas, Undergraduate Student Mr. Michael Gurevich, High School Student Ms. Amy Varghese, High School Student 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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| from left: Man Liu,
Yuson Chong, Claire Mettewie, Jim Dilger |
June 2008 - Demazumder (Deep) Deeptanker accepted to John's Hopkins
clinical cardiology training program
January 2008 - Mandy Liu moves to University of Illinois, Chicago
August 2007 - Yuson Chong steps down to begin NYU Nursing School
August 18, 2005 - Ana Maria Vidal retires after 16 outstanding years
October 18, 2005 - Yuson Chong joins the group as a Research Support Specialist
October 21, 2005 - Bonnie Lam and Lana Castor named as Siemens Westinghouse Competition semifinalists
October 31, 2005 - Bonnie Lam and Lana Castor named as Siemens Westinghouse Competition Middle States Regional Finalists|
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. |
 |
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. [abstract]
I. Wenningmann and
J.P. Dilger.
Die Kinetik der Inhibition nichtdepolarisierender Muskelrelaxantien am
nikotinergen Acetylcholinrezeptor.
Anasthesiol Intensivmed Notfallmed Schmerzther. 35:607-608, 2000
[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. [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. [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 Pharmacology60: 584-594, 2001. [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. [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. [abstract]
[full
text] [pdf]
