| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* To whom correspondence should be addressed. E-mail: bennettd{at}ualberta.ca.
Following chronic spinal cord injury motoneurons exhibit large plateau potentials (sustained depolarizations triggered by brief inputs) that play a primary role in the development of muscle spasms and spasticity (Bennett et al. 2001a,b). The present study examined the voltage-gated persistent inward currents (PICs) underlying these plateaus. Adult rats were spinalized at the S2 sacral spinal level and after two months (when spasticity developed) intracellular recordings were made from motoneurons below the injury. For recording, the whole sacrocaudal spinal cord was removed and maintained in vitro in normal artificial cerebral spinal fluid (nACSF), without application of neuromodulators. During a slow triangular voltage-clamp command (ramp) a PIC was activated with a threshold of -54.2 ± 4.8 mV (similar to plateau threshold), peak current of 2.88 ± 0.95 nA and produced a pronounced negative-slope region in the V-I relation. This PIC was in part mediated by Cav1.3 L-type calcium channels, because it was low threshold and significantly reduced by 10 to 20 µM nimodipine or 400 µM Cd++. The PIC that remained during a calcium channel blockade (in Cd++) was completely and rapidly blocked by TTX (0.5 to 2 µM), and thus was a TTX-sensitive persistent sodium current. This persistent sodium current was activated rapidly about 7 mV below the spike threshold (spike threshold -46.1 ± 4.5 mV), contributed ~1/2 of the initial peak of the total PIC, inactivated partly to contribute only ~1/3 of the sustained PIC (at 5 to 10 sec), and deactivated rapidly with hyperpolarization (< 50 ms). When TTX was added to the bath first, the nimodipine-sensitive persistent calcium current (L-type) was seen in isolation; it was slowly activated (> 250 ms), had a low but variable threshold (either above or below the spike threshold), contributed the other ~1/2 of the initial peak of the total PIC (prior to TTX), did not usually inactivate with time (contributed ~2/3 of the sustained PIC), and deactivated slowly with hyperpolarization to rest (in > 300 ms). In summary, low-threshold persistent calcium (Cav1.3) and sodium currents spontaneously develop in motoneurons of chronic spinal rats and these enable large, rapidly activated plateaus that ultimately lead to spasticity.
This article has been cited by other articles:
|
|
 |
|
  J. S. Carp, A. M. Tennissen, D. L. Mongeluzi, C. J. Dudek, X. Y. Chen, and J. R. Wolpaw An In Vitro Protocol for Recording From Spinal Motoneurons of Adult Rats J Neurophysiol, July 1, 2008; 100(1): 474 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Dougherty and S. Hochman Spinal Cord Injury Causes Plasticity in a Subpopulation of Lamina I GABAergic Interneurons J Neurophysiol, July 1, 2008; 100(1): 212 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Gradwohl and Y. Grossman Analysis of the interaction between the dendritic conductance density and activated area in modulating alpha-motoneuron EPSP: statistical computer model. Neural Comput., June 1, 2008; 20(6): 1385 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.J. Heckman, M. Johnson, C. Mottram, and J. Schuster Persistent Inward Currents in Spinal Motoneurons and Their Influence on Human Motoneuron Firing Patterns Neuroscientist, June 1, 2008; 14(3): 264 - 275. [Abstract] [PDF]
|
|
|
|
 |
|
 J. A. Norton, D. J. Bennett, M. E. Knash, K. C. Murray, and M. A. Gorassini Changes in sensory-evoked synaptic activation of motoneurons after spinal cord injury in man Brain, June 1, 2008; 131(6): 1478 - 1491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Bennett Demystifying Spasticity: Reply to Dietz J Neurophysiol, February 1, 2008; 99(2): 1041 - 1043. [Full Text] [PDF]
|
|
|
|
|
|
T. V. Bui, G. Grande, and P. K. Rose Multiple Modes of Amplification of Synaptic Inhibition to Motoneurons by Persistent Inward Currents J Neurophysiol, February 1, 2008; 99(2): 571 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. V. Bui, G. Grande, and P. K. Rose Relative Location of Inhibitory Synapses and Persistent Inward Currents Determines the Magnitude and Mode of Synaptic Amplification in Motoneurons J Neurophysiol, February 1, 2008; 99(2): 583 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Button, J. M. Kalmar, K. Gardiner, T. Marqueste, H. Zhong, R. R. Roy, V. R. Edgerton, and P. F. Gardiner Does elimination of afferent input modify the changes in rat motoneurone properties that occur following chronic spinal cord transection? J. Physiol., January 15, 2008; 586(2): 529 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Manuel, C. Meunier, M. Donnet, and D. Zytnicki Resonant or Not, Two Amplification Modes of Proprioceptive Inputs by Persistent Inward Currents in Spinal Motoneurons J. Neurosci., November 21, 2007; 27(47): 12977 - 12988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Brownstone Take Your PIC: Motoneuronal Persistent Inward Currents May Be Somatic as Well as Dendritic. Focus on "Facilitation of Somatic Calcium Channels Can Evoke Prolonged Tail Currents in Rat Hypoglossal Motoneurons" J Neurophysiol, August 1, 2007; 98(2): 579 - 580. [Full Text] [PDF]
|
|
|
|
|
|
S. Tazerart, J.-C. Viemari, P. Darbon, L. Vinay, and F. Brocard Contribution of Persistent Sodium Current to Locomotor Pattern Generation in Neonatal Rats J Neurophysiol, August 1, 2007; 98(2): 613 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Tan, H. P. Theeuwes, L. Feenstra, and J.G.G. Borst Membrane Properties and Firing Patterns of Inferior Colliculus Neurons: An In Vivo Patch-Clamp Study in Rodents J Neurophysiol, July 1, 2007; 98(1): 443 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. ElBasiouny and V. K. Mushahwar Modulation of motoneuronal firing behavior after spinal cord injury using intraspinal microstimulation current pulses: a modeling study J Appl Physiol, July 1, 2007; 103(1): 276 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. P. Shapiro and R. H. Lee Synaptic Amplification Versus Bistability in Motoneuron Dendritic Processing: A Top-Down Modeling Approach J Neurophysiol, June 1, 2007; 97(6): 3948 - 3960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Grande, T. V. Bui, and P. K. Rose Estimates of the Location of L-type Ca2+ Channels in Motoneurons of Different Sizes: A Computational Study J Neurophysiol, June 1, 2007; 97(6): 4023 - 4035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li and D. J. Bennett Apamin-Sensitive Calcium-Activated Potassium Currents (SK) Are Activated by Persistent Calcium Currents in Rat Motoneurons J Neurophysiol, May 1, 2007; 97(5): 3314 - 3330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Rank, X. Li, D. J. Bennett, and M. A. Gorassini Role of Endogenous Release of Norepinephrine in Muscle Spasms After Chronic Spinal Cord Injury J Neurophysiol, May 1, 2007; 97(5): 3166 - 3180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Theiss, J. J. Kuo, and C. J. Heckman Persistent inward currents in rat ventral horn neurones J. Physiol., April 15, 2007; 580(2): 507 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Button, J. M. Kalmar, K. Gardiner, F. Cahill, and P. F. Gardiner Spike frequency adaptation of rat hindlimb motoneurons J Appl Physiol, March 1, 2007; 102(3): 1041 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, K. Murray, P. J. Harvey, E. W. Ballou, and D. J. Bennett Serotonin Facilitates a Persistent Calcium Current in Motoneurons of Rats With and Without Chronic Spinal Cord Injury J Neurophysiol, February 1, 2007; 97(2): 1236 - 1246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Smith and J.-F. Perrier Intrinsic Properties Shape the Firing Pattern of Ventral Horn Interneurons From the Spinal Cord of the Adult Turtle J Neurophysiol, November 1, 2006; 96(5): 2670 - 2677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Harvey, Y. Li, X. Li, and D. J. Bennett Persistent Sodium Currents and Repetitive Firing in Motoneurons of the Sacrocaudal Spinal Cord of Adult Rats J Neurophysiol, September 1, 2006; 96(3): 1141 - 1157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Harvey, X. Li, Y. Li, and D. J. Bennett 5-HT2 Receptor Activation Facilitates a Persistent Sodium Current and Repetitive Firing in Spinal Motoneurons of Rats With and Without Chronic Spinal Cord Injury J Neurophysiol, September 1, 2006; 96(3): 1158 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Harvey, X. Li, Y. Li, and D. J. Bennett Endogenous Monoamine Receptor Activation Is Essential for Enabling Persistent Sodium Currents and Repetitive Firing in Rat Spinal Motoneurons J Neurophysiol, September 1, 2006; 96(3): 1171 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Kuo, R. H. Lee, L. Zhang, and C. J. Heckman Essential role of the persistent sodium current in spike initiation during slowly rising inputs in mouse spinal neurones J. Physiol., August 1, 2006; 574(3): 819 - 834. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Button, K. Gardiner, T. Marqueste, and P. F. Gardiner Frequency-current relationships of rat hindlimb {alpha}-motoneurones J. Physiol., June 15, 2006; 573(3): 663 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Hornby, J. H. Kahn, M. Wu, and B. D. Schmit Temporal facilitation of spastic stretch reflexes following human spinal cord injury J. Physiol., March 15, 2006; 571(3): 593 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Le, D. R. Verley, J.-M. Goaillard, D. I. Messinger, A. E. Christie, and J. T. Birmingham Bistable Behavior Originating in the Axon of a Crustacean Motor Neuron J Neurophysiol, March 1, 2006; 95(3): 1356 - 1368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. ElBasiouny, D. J. Bennett, and V. K. Mushahwar Simulation of Ca2+ persistent inward currents in spinal motoneurones: mode of activation and integration of synaptic inputs J. Physiol., January 15, 2006; 570(2): 355 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. V. Bui, M. Ter-Mikaelian, D. Bedrossian, and P. K. Rose Computational Estimation of the Distribution of L-type Ca2+ Channels in Motoneurons Based on Variable Threshold of Activation of Persistent Inward Currents J Neurophysiol, January 1, 2006; 95(1): 225 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. ElBasiouny, D. J. Bennett, and V. K. Mushahwar Simulation of Dendritic CaV1.3 Channels in Cat Lumbar Motoneurons: Spatial Distribution J Neurophysiol, December 1, 2005; 94(6): 3961 - 3974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Kocsis, S. Farkas, L. Fodor, N. Bielik, M. Than, S. Kolok, A. Gere, M. Csejtei, and I. Tarnawa Tolperisone-Type Drugs Inhibit Spinal Reflexes via Blockade of Voltage-Gated Sodium and Calcium Channels J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1237 - 1246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Floeter, P. Zhai, R. Saigal, Y. Kim, and J. Statland Motor Neuron Firing Dysfunction in Spastic Patients With Primary Lateral Sclerosis J Neurophysiol, August 1, 2005; 94(2): 919 - 927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B Miles, Y Dai, and R. M Brownstone Mechanisms underlying the early phase of spike frequency adaptation in mouse spinal motoneurones J. Physiol., July 15, 2005; 566(2): 519 - 532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J Kuo, T Siddique, R Fu, and C. J Heckman Increased persistent Na+ current and its effect on excitability in motoneurones cultured from mutant SOD1 mice J. Physiol., March 15, 2005; 563(3): 843 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Derjean, S Bertrand, F Nagy, and S. J Shefchyk Plateau potentials and membrane oscillations in parasympathetic preganglionic neurones and intermediolateral neurones in the rat lumbosacral spinal cord J. Physiol., March 1, 2005; 563(2): 583 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-F. Perrier and M. C. Tresch Recruitment of motor neuronal persistent inward currents shapes withdrawal reflexes in the frog J. Physiol., January 15, 2005; 562(2): 507 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lipscombe, T. D. Helton, and W. Xu L-Type Calcium Channels: The Low Down J Neurophysiol, November 1, 2004; 92(5): 2633 - 2641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, X. Li, P. J. Harvey, and D. J. Bennett Effects of Baclofen on Spinal Reflexes and Persistent Inward Currents in Motoneurons of Chronic Spinal Rats With Spasticity J Neurophysiol, November 1, 2004; 92(5): 2694 - 2703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Mee, E. C. G. Pym, K. G. Moffat, and R. A. Baines Regulation of Neuronal Excitability through Pumilio-Dependent Control of a Sodium Channel Gene J. Neurosci., October 6, 2004; 24(40): 8695 - 8703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Gorassini, M. E. Knash, P. J. Harvey, D. J. Bennett, and J. F. Yang Role of motoneurons in the generation of muscle spasms after spinal cord injury Brain, October 1, 2004; 127(10): 2247 - 2258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. Hart and S. F. Giszter Modular Premotor Drives and Unit Bursts as Primitives for Frog Motor Behaviors J. Neurosci., June 2, 2004; 24(22): 5269 - 5282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Valero-Cabre, J. Fores, and X. Navarro Reorganization of Reflex Responses Mediated by Different Afferent Sensory Fibers After Spinal Cord Transection J Neurophysiol, June 1, 2004; 91(6): 2838 - 2848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, P. J. Harvey, X. Li, and D. J. Bennett Spastic Long-Lasting Reflexes of the Chronic Spinal Rat Studied In Vitro J Neurophysiol, May 1, 2004; 91(5): 2236 - 2246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Bennett, L. Sanelli, C. L. Cooke, P. J. Harvey, and M. A. Gorassini Spastic Long-Lasting Reflexes in the Awake Rat After Sacral Spinal Cord Injury J Neurophysiol, May 1, 2004; 91(5): 2247 - 2258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, M. A. Gorassini, and D. J. Bennett Role of Persistent Sodium and Calcium Currents in Motoneuron Firing and Spasticity in Chronic Spinal Rats J Neurophysiol, February 1, 2004; 91(2): 767 - 783. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
