Endogenous Monoamine Receptor Activation Is Essential for Enabling Persistent Sodium Currents and Repetitive Firing in Rat Spinal Motoneurons

Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada Submitted 31 March 2006; accepted in final form 31 May 2006 The spinal cord and spinal motoneurons are densely innervated by terminals of serotonin (5-HT) and norepinephrine (NE) neurons arising mostly from the brain stem, but...

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Published in:Journal of neurophysiology 2006-09, Vol.96 (3), p.1171-1186
Main Authors: Harvey, P. J, Li, X, Li, Y, Bennett, D. J
Format: Article
Language:English
Subjects:
Animals
Female
Motor Neurons - drug effects
Motor Neurons - physiology
Norepinephrine - physiology
Patch-Clamp Techniques
Picrotoxin - pharmacology
Rats
Rats, Sprague-Dawley
Serotonin - physiology
Sodium Channels - drug effects
Sodium Channels - physiology
Spinal Cord - physiology
Spinal Cord - physiopathology
Spinal Cord Injuries - physiopathology
Strychnine - pharmacology
Synaptic Transmission - drug effects
Synaptic Transmission - physiology
Tetrodotoxin - pharmacology
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Summary:Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada Submitted 31 March 2006; accepted in final form 31 May 2006 The spinal cord and spinal motoneurons are densely innervated by terminals of serotonin (5-HT) and norepinephrine (NE) neurons arising mostly from the brain stem, but also from intrinsic spinal neurons. Even after long-term spinal transection (chronic spinal), significant amounts (10%) of 5-HT and NE (monoamines) remain caudal to the injury. To determine the role of such endogenous monoamines, we blocked their action with monoamine receptor antagonists and measured changes in the sodium currents and firing in motoneurons. We focused on persistent sodium currents (Na PIC) and sodium spike properties because they are critical for enabling repetitive firing in motoneurons and are facilitated by monoamines. Intracellular recordings were made from motoneurons in the sacrocaudal spinal cord of normal and chronic spinal rats (2 mo postsacral transection) with the whole sacrocaudal cord acutely removed and maintained in vitro (cords from normal rats termed acute spinal ). Acute and chronic spinal rats had TTX-sensitive Na PICs that were respectively 0.62 ± 0.76 and 1.60 ± 1.04 nA, with mean onset voltages of –63.0 ± 5.6 and –64.1 ± 5.4 mV, measured with slow voltage ramps. Application of 5-HT 2A , 5-HT 2C , and 1-NE receptor antagonists (ketanserin, RS 102221, and WB 4101, respectively) significantly reduced the Na PICs, and a combined application of these three monoamine antagonists completely eliminated the Na PIC, in both acute and chronic spinal rats. Likewise, reduction of presynaptic transmitter release (including 5-HT and NE) with long-term application of cadmium also eliminated the Na PIC. Associated with the elimination of the Na PIC in monoamine antagonists, the motoneurons lost their ability to fire during slow current ramps. At this point, the spike evoked by antidromic stimulation was not affected, suggesting that activation of the transient sodium current was not impaired. However, the spike evoked after a slow ramp depolarization was slightly reduced in height and rate-of-rise, suggesting decreased sodium channel availability as a result of increased channel inactivation. These results suggest that endogenous monoamine receptor activation is critical for enabling the Na PIC and decreasing sodium channel inactivation, ultimately enabling steady repetitive firing in both normal and chronic spinal rats. Address for repri
ISSN:0022-3077
1522-1598
DOI:10.1152/jn.00341.2006