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The Journal of Neurophysiology Vol. 86 No. 5 November 2001, pp. 2173-2182
Copyright ©2001 by the American Physiological Society
1-Noradrenergic Receptors in Rat Olfactory Bulb Slices
Department of Anatomy and Neurobiology, Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201
Hayar, Abdallah,
Phillip M. Heyward,
Thomas Heinbockel,
Michael T. Shipley, and
Matthew Ennis.
Direct Excitation of Mitral Cells Via Activation of
1-Noradrenergic Receptors in Rat Olfactory Bulb Slices. J. Neurophysiol. 86: 2173-2182, 2001. The main olfactory bulb
receives a significant modulatory noradrenergic input from the locus
coeruleus. Previous in vivo and in vitro studies showed that
norepinephrine (NE) inputs increase the sensitivity of mitral cells to
weak olfactory inputs. The cellular basis for this action of NE
is not understood. The goal of this study was to investigate the effect
of NE and noradrenergic agonists on the excitability of mitral cells,
the main output cells of the olfactory bulb, using whole cell
patch-clamp recording in vitro. The noradrenergic agonists,
phenylephrine (PE, 10 µM), isoproterenol (Isop, 10 µM), and
clonidine (3 µM), were used to test for the functional presence of
1-,
-, and
2-receptors, respectively, on mitral cells. None of
these agonists affected olfactory nerve (ON)-evoked field potentials
recorded in the glomerular layer, or ON-evoked postsynaptic currents
recorded in mitral cells. In whole cell voltage-clamp recordings, NE
(30 µM) induced an inward current (54 ± 7 pA, n = 16) with an EC50 of 4.7 µM. Both PE and Isop
also produced inward currents (22 ± 4 pA, n = 19, and 29 ± 9 pA, n = 8, respectively), while
clonidine produced no effect (n = 6). In the presence
of TTX (1 µM), and blockers of excitatory and inhibitory fast
synaptic transmission [gabazine 5 µM,
6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) 10 µM, and
(±)-2-amino-5-phosphonopentanoic acid (APV) 50 µM], the
inward current induced by PE persisted (EC50 = 9 µM), whereas that of Isop was absent. The effect of PE was also
observed in the presence of the Ca2+ channel
blockers, cadmium (100 µM) and nickel (100 µM). The inward current
caused by PE was blocked when the interior of the cell was perfused
with the nonhydrolyzable GDP analogue, GDP
S, indicating that the
1 effect is mediated by G-protein coupling. The current-voltage relationship in the absence and presence of PE indicated that the
current induced by PE decreased near the equilibrium potential for
potassium ions. In current-clamp recordings from bistable mitral cells,
PE shifted the membrane potential from the downstate (
52 mV) toward
the upstate (
40 mV), and significantly increased spike generation in
response to perithreshold ON input. These findings indicate that NE
excites mitral cells directly via
1 receptors, an effect that may
underlie, at least in part, increased mitral cell responses to weak ON
input during locus coeruleus activation in vivo.
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