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Centre for Neuroscience, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
Submitted 11 March 2003; accepted in final form 21 April 2003
After 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 2 mo, 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), with a 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 Cd2+. The PIC that remained during a calcium channel blockade (in Cd2+) was completely and rapidly blocked by tetrodotoxin (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 approximately 1/2 of the initial peak of the total PIC, inactivated partly to contribute only approximately 1/3 of the sustained PIC (at 5 to 10 s), 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 slightly above or below the spike threshold), contributed the other approximately 1/2 of the initial peak of the total PIC (before TTX), did not usually inactivate with time (contributed approximately two-thirds 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.
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