Soleus muscle length, stretch reflex excitability, and the contractile properties of muscle in children and adults: a study of the functional joint angle

The influence of the joint angle on stretch reflex excitability of the soleus muscle at the ankle has been studied in 22 children aged 3.9 to 13.6 years and 9 adults aged 19 to 70 years. For all subjects, reflex EMG and mechanical twitch torque gain were trivial at resting plantar flexion. The reflex EMG gain reached a maximum between-15^o and-10^o of plantar flexion beyond the neutral angle, 0^o, denned as the foot at right angle to the tibia, diminishing steeply with further dorsiflexion. The reflex mechanical gain rose to a peak between 0^o and +10^o of dorsiflexion beyond neutral, declining steeply thereafter. By contrast, axonally stimulated muscle twitch torque increased serially up to +30^o dorsiflexion beyond neutral. For the soleus muscle, the optimal reflex neuromechanical angle lies approximately midway between the angle for optimal reflex EMG gain (in mild plantar flexion, at which the largest and strongest motor units can be activated) and the optimal muscle mechanical angle (at the extreme of soleus muscle dorsiflexion). These studies confirm that the excitability of the spinal alpha motor neuron pool in vivo is strongly influenced by muscle length and explain the variability in reflex excitability within and between subjects, if the joint angle is not controlled. They also indicate how posture influences movement, agreeing with the known function of the soleus muscle in the stance phase of gait and the modulation of motor unit recruitment during voluntary alternating movements at the ankle. Soleus muscle twitch characteristics show a fivefold to eightfold increase in peak force associated with a tenfold reduction in compliance in the first two decades of life and an apparent speeding up of twitch time in the first decade.     

The progression of untreated lumbar kyphosis and the compensatory thoracic lordosis in myelomeningocele

Radiographs of 37 patients with untreated lumbar kyphosis without congenital vertebral anomalies associated with myelomeningocele were analyzed. With an average interval between radiographs of 6.2 years, the kyphosis was noted to increase at a mean rate of 4.3^o per year without correlation to its initial magnitude. The compensatory lordosis was more variable and progressed at a mean of 2.5^o per year. Children under the age of 2 years were more likely to increase the Cobb angle and the height of their kyphosis. There was an inverse relationship between the height of the kyphus and the lumbar spine height and the resultant growth of each. A modified kyphotic index less than 4. correlated with an increase in the curve and height of the kyphosis and the subsequent desire for surgery. Wide variablity in radiographic parameters make predictions for an individual patient difficult.     

Musculoskeletal modelling in determining the effect of botulinum toxin on the hamstrings of patients with crouch gait

This study aimed to determine the effect of hamstring botulinum toxin A (Btx-A) injection in 10 children with crouch gait in terms of changes in muscle length and lower-limb kinematics. Before Btx-A injection limb kinematics were recorded. Maximum hamstring lengths and excursions were calculated by computer modelling of the lower limb. Data were compared with the averaged hamstring lengths of 10 control children. Hamstrings were denned as short if their length was shorter than the average maximum length minus one standard deviation. Gait analysis was repeated 2 weeks after isolated hamstring Btx-A injection. Pre- and postinjection kinematic data and muscle lengths were then compared. Four of 18 injected limbs in three subjects had short medial hamstring before injection, none of the subjects had short lateral hamstrings. Muscle excursion was significantly reduced in the short and adequate maximum muscle length groups. A significant increase in the semimembranosus and semitendinosus length in all of the injected limbs was noted. Only in the short muscle group was a significant increase in muscle excursion observed. Knee extension improved by 13° in the adequate muscle length group and by 15.6° in the short muscle length group. Pelvic tilt and hip flexion increased in both groups non-significantly. Average walking speed postinjection increased from 0.60 ms^-1 to 0.71 ms^-1. Short hamstrings are over-diagnosed in crouch gait. Hamstring Btx-A injection in patients with crouch gait produces significant, repeatable muscle lengthening and improved ambulatory function.     

Lumbar hyperlodosis in cerebral palsy: anatomic analysis and surgical strategy for correction

Introduction We report our experience of five cases in adolescents with spastic quadriplegia who had primarily sagittal plane deformity with hyperlordosis of the lumbar spine, an uncommon condition in cerebral palsy spinal deformity.Methods Three boys and two girls, 13 to 19 years old, were surgically treated for excessive lumbar lordosis which made sitting difficult. Bilateral hip flexion contractures were present in all cases with a very horizontal sacrum and, in four cases, associated with pelvic anteversion. Two patients were surgically treated by posterior spinal fusion and instrumentation, and three patients had anterior discectomy and fusion prior to posterior fusion and instrumentation.Conclusion Hyperlordosis was reduced by 26 to 48°, and the horizontal sacrum was corrected by 15 to 35°, which enabled the patients to sit comfortably.     

The cutaneous contribution to the hamstring flexor reflex in the rat: an electrophysiological and anatomical study

The location and properties of the cutaneous receptive fields responsible for detecting the flexor withdrawal reflex in the posterior head of biceps femoris (pBF) and semitendinosus (ST) components of the hamstring muscle have been examined in unanaesthetized decerebrate rats, spinalized at T10-T11. Single alpha-motoneurone efferents were recorded from the nerve to pBF and the principal head of ST and their responses to ipsi- and contralateral hindlimb skin stimulation investigated. The efferents to both muscles characteristically had a low or absent background discharge and they all had mechanoreceptive fields on the ipsilateral foot. The mechanical threshold of these fields was high with no response to light touch or brush. Fifty-four percent of these units also had a smaller and weaker contralateral mechanoreceptive field. The only apparent difference between ST and pBF efferents was that more ST efferents had contralateral fields than pBF units. Noxious, hot and cold thermal stimuli applied to the ipsilateral foot activated 56% of the efferents. Mustard oil, a chemical irritant, produced a long-lasting flexor response when applied to the ipsilateral foot. The responses of these efferents to stimulation of A beta, A delta and C cutaneous afferents in the sural nerve were also studied. Short latency reflexes were elicited in all efferents by A beta inputs, longer latency reflexes were elicited in 64% by A delta inputs and very long latency responses with long afterdischarges were found in 73% of the units to C inputs. Retrograde labelling of the hamstring motoneurones with WGA-HRP indicated that they lay in ventrolateral lamina IX extending from the caudal portion of the third lumbar segment to the junction of the 5th and 6th lumbar segments. Transganglionic labelling of small diameter primary afferent terminals in the dorsal horn of cutaneous nerves innervating the foot revealed that the longitudinal distribution corresponded closely with that of the hamstring motor nucleus. The flex-or reflex in the spinal rat provides a useful model therefore, for studying how the input in nociceptive afferents is processed and transformed within the spinal cord, to produce appropriate outputs.     

A new device for internal fixation of thoracolumbar and lumbar spine fractures: the 'fixateur interne'

A new system of operative fixation of thoracolumbar and lumbar spine fractures is presented: the 'fixateur interne' (F.I.). From a posterior approach long Schanz screws are inserted through the pedicles into the body of the two vertebrae just adjacent to the lesion and connected by th threaded F.I. rods. By tightening the nuts the Schanz screws are fixed in all directions. The advantages of the F.I. system are: excellent reposition by the long lever-arm of the Schanz screws, immobilization of only two segments and therefore good mobility of the residual spine, stability against flexion forces better than is obtained with Harrington distraction rods, additional rotational stability, and fixation in lordosis or kyphosis as is desired. The F.I. does not act as a four point bending system like all other dorsal spine instrumentation systems, but provides stability in flexion by itself. Therefore it can be Used independently of the condition of all ligaments (including the anterior longitudinal ligament) and of the posterior wall of the fractured vertebrae, and there is no need to fix more than the two immediately adjacent vertebrae, thus avoiding the often painful and cumbersome iatrogenic loss of lumbar lordosis and of mobility and permitting early mobilization of the patient. Experience with the first 45 patients is very promising.     

Gait Electromyography in Normal and Spastic Children, with Special Reference to Quadriceps Femoris and Hamstring Muscles

Telemetered gait electromyography was used to investigate gait patterns and the phasic behavior of the quadriceps femoris and medial hamstring muscles in 26 normal children and 32 children with spastic cerebral palsy. The average child with spastic cerebral palsy was found to have a shorter stance phase than the normal, but the cadence, while more variable, was nearly the same as normal. The spastic muscles typically exhibited prolonged phasic activity or a dysphasic pattern. Most of the patients with spastic hamstrings also had spastic quadriceps, suggesting that over-weakening the hamstrings may produce an unwanted genu recurvatum or hyperextended knee gait. Care must be taken to balance hamstring spasticity with quadriceps spasticity. A final result with slight knee flexion is preferable to hyperextension.     

The BioFlex System as a Dynamic Stabilization Device : Does It Preserve Lumbar Motion?

Objective

This study examines whether functional motion is present at one or more years after Bioflex System placement. BioFlex System is a flexible rod system which has been used to preserve motion at the area of implantation. There has not been a scientific study showing how much motion is preserved after implantation.

Methods

A total of 12 consecutive patients underwent posterior dynamic stabilization using the BioFlex System. Six patients were treated using a L3-4-5 construct and other six patients using a L4-5-S1 construct. Follow-up ranged from 12 to 33 months and standing neutral lateral, extension, flexion and posteroanterior (PA) radiographs were obtained at 3, 6, 9, and 12 months and at more than 12 months postoperatively. Range of motion (ROM), whole lumbar lordosis, and ROMs of motion segments from L2 to S1 were determined.

Results

Patients with a L3-4-5 construct demonstrated a decrease in mean ROM for whole lumbar decreased from 40.08 to 30.77. Mean ROM for L3-4 (6.12 to 2.20) and L4-5 (6.55 to 1.67) also decreased after one year. Patients with a L4-5-S1 construct demonstrated L4-5 (8.75 to 2.70) and L5-S1 (9.97 to 3.25) decrease of mean ROM at one year postoperatively. Lumbar lordosis was preserved at both L3-4-5 and L4-5-S1 constructs. Clinical results showed significant improvements in both study groups.

Conclusion

The present study provides preliminary information regarding the BioFlex motion preservation system. We conclude that the BioFlex System preserves functional motion to some degree at instrumented levels. However, although total lumbar lordosis was preserved, ROMs at implantation segments were lower than preoperative values.     

p21ras Oncogene Protein Selectively Increases Low-voltage-activated Ca2+ Current Density in Embryonic Chick Dorsal Root Ganglion Neurons

p21^ras protein resembles the α subunit of trimeric G-proteins, which regulate ion channel function. We now report a modulation of Ca²⁺ channels in vertebrate sensory neurons by p21^ras in addition to its role in cell growth and differentiation. Quantitative microinjection of oncogenic p21-H-ras into embryonic chick dorsal root ganglion neurons was performed. After 4 h the current density of the low-voltage-activated (LVA; T-type) Ca²⁺ channels was increased. However, in contrast to trimeric G-proteins, which inhibit high-voltage-activated (HVA) Ca²⁺ channels in chick dorsal root ganglion neurons, p21^ras did not significantly affect HVA Ca²⁺ currents. To study the time course of p21^ras action, guanosine triphosphate-preloaded p21^ras was added to the patch pipette. Full-length ras was effective only after a delay of 20 -30 min. C-terminal modification by cellular enzymes is required to activate full-length ras, and can account for the observed delay. Unexpectedly, C-terminal-truncated p2l^ras, which was found to be inactive in biological assays, enhanced LVA Ca²⁺ currents within minutes. This suggests a G-protein-like modulation of the LVA Ca²⁺ channel by p21^ras. In an early phase of neuronal differentiation, dorsal root ganglion neurons express only LVA Ca²⁺ currents. The regulatory role of p21^ras on LVA channels may therefore be particularly important during differentiation.     

The outcome of walking in stable neuromuscular deficiencies

In some patients with stable or very gradually worsening neuromuscular disorders, walking performance nevertheless decreases with increasing hip flexion and spinal deformity as the patient grows. The relations between muscular deficiency, pelvic and spinal deformity, head stability, gravit; parameters and walking performance were studied in 43 patients aged 18 months to 38 years with a view to finding out how these parameters are related, whether progressive spinal deformity and loss of walking can be avoided or delayed, and whether specific therapy for each of these parameters can help. Early combating of hip flexion deformity by physiotherapy, accompanied by limbering-up exercises of the spine to counteract lumbar and thoracic lordosis are useful, as are orthoses to correct pelvic tilt anteversion, spinal lordosis and head instability. If physiotherapy is ineffectual or too late, tenoctomy of the rectus femoris may help.     

A comparison study on the change in lumbar lordosis when standing, sitting on a chair, and sitting on the floor in normal individuals

Objective

To compare radiographic analysis on the sagittal lumbar curve when standing, sitting on a chair, and sitting on the floor.

Methods

Thirty asymptomatic volunteers without a history of spinal pathology were recruited. The study population comprised 11 women and 19 men with a mean age of 29.8 years. An independent observer assessed whole lumbar lordosis (WL) and segmental lordosis (SL) between L1 and S1 using the Cobb''s angle on lateral radiographs of the lumbar spine obtained from normal individuals when standing, sitting on a chair, and sitting on the floor. WL and SL at each segment were compared for each position.

Results

WL when sitting on the floor was reduced by 72.9% than the average of that in the standing position. Of the total decrease in WL, 78% occurred between L4 to S1. There were significant decreases in SL at all lumbar spinal levels, except L1-2, when sitting on the floor as compared to when standing and sitting on a chair. Changes in WL between the positions when sitting on a chair and when sitting on the floor were mostly contributed by the loss of SL at the L4-5 and L5-S1 levels.

Conclusion

When sitting on the floor, WL is relatively low; this is mostly because of decreasing lordosis at the L4-5 and L5-S1 levels. In the case of lower lumbar fusion, hyperflexion is expected at the adjacent segment when sitting on the floor. To avoid this, sitting with a lordotic lumbar curve is important. Surgeons should remember to create sufficient lordosis when performing lower lumbar fusion surgery in patients with an oriental life style.     

Effect of dynamic orthoses on gait: a retrospective control study in children with hemiplegia

Several positive influences of orthoses on gait in children with cerebral palsy have been documented, as well as some detrimental effects. Most importantly, push-off is decreased in orthoses, compromising a physiological third ankle rocker. The aim of this study was to evaluate the effect of three types of orthosis on gait in a homogeneous group of children. All orthoses aimed at improving push-off and normalizing the pathological plantarflexion-knee extension couple. Thirty-seven children (22 females, 15 males) with hemiplegia, aged 4 to 10 years (30 Gross Motor Function Classification System [GMFCS] Level I, six GMFCS Level II), walked barefoot and with orthoses being either Orteams (orthoses with the dorsal part containing 11 sleeves), posterior leafsprings (PLS), or Dual Carbon Fibre Spring ankle foot orthosis (AFOs; CFO: carbon fibre at the dorsal part of the orthosis). All orthoses were expected to prevent plantarflexion and allow dorsiflexion, thus improving first, second, and third rocker. The orthoses were compared through objective gait analysis, including 3D kinematics and kinetics. All orthoses successfully improved the gait pattern and only small differences were noted between the configurations of the different orthoses. The CFO, however, allowed a more physiological third ankle rocker compared with the Orteam/PLS. Although the PLS ensured the highest correction at the ankle around initial contact, the CFO created a significantly higher maximal hip flexion moment in stance. In general, the results of this study indicated a substantial functional flexibility of the CFO.     

Speed and Efficiency in Walking and Wheeling with Novel Stimulation and Bracing Systems After Spinal Cord Injury: A Case Study

To compare various novel and conventional systems for locomotion, a 25‐year‐old man was studied with motor complete spinal cord injury at the T4/5 level. He used various devices in the community, and changes in speed, physiological cost index (PCI), and oxygen consumption were measured periodically. Speed was fastest with a conventional manual wheelchair (nearly 120 m/min in a 4‐min test). Speed was about 30% less, but the PCI was lowest (highest efficiency) using functional electrical stimulation (FES) of the quadriceps and hamstring muscles to propel a novel wheelchair. He walked with knee‐ankle‐foot orthoses (KAFO) at much lower speed (8.8 m/min) and higher PCI. He walked with an alternating gait using a new stance‐control KAFO with FES. The speed was still slow (5 m/min), but he prefers the more normal‐looking gait and uses it daily. Walking with FES and ankle‐foot orthoses (AFO) was slowest (3.5 m/min) and had the highest PCI. In conclusion, the leg‐propelled wheelchair provides a more efficient method of locomotion. A new stance‐controlled KAFO with FES may provide a more acceptable walking system, but must be tested on other subjects.     

Intracellular Chloride Activity and the Effect of 5-Hydroxytryptamine on the Chloride Conductance of Leech Retzius Neurons

Intracellular Cl^- activity (aClⁱ) and 5-hydroxytryptamine (5-HT)-induced membrane currents of Retzius neurons in the central nervous system of the medicinal leech were measured using Cl^- sensitive microelectrodes and a two-microelectrode voltage-clamp technique. At the membrane of Retzius neurons Cl^- ions were not passively distributed. Under different conditions the chloride equilibrium potential (E^Cl, -60.1 mV for isotonic saline and -57.8 mV for a hypertonic saline) was negative with respect to the membrane potential (E_m-55 ± 3.8 and -47 ± 3.4 mV respectively). The endogenous neurohormone 5-HT always polarized the membrane of Retzius neurons in the direction of E^Cl. When voltage-clamping the membrane of Retzius neurons near the resting potential both in situ and in primary culture, application of 5-HT produced an outward current ( l _5-HT) and increase in membrane conductance. Current - voltage relationships for l _5-HTshowed a slight outward rectification and reversal potentials of -61.6± 3.1 mV in situ and -66± 3.1 mV in primary culture, both values being comparable to the E_cl of Retzius neurons as measured in situ . The results indicate that 5-HT increases the Cl^- conductance of Retzius neurons, thereby hyperpolarizing the cell membrane and affecting both the excitability of the neuron and 5-HT release from it. This could affect the feeding and swimming behaviour of the leech.     

Treatment of knee contracture in cerebral palsy by hamstring lengthening, posterior capsulotomy, and quadriceps mechanism shortening

Results of surgery to correct fixed flexion contracture of the knee and improve voluntary knee extension in 39 knees in 20 children (11 females, 9 males; mean age 12 years 8 months, age range 5 to 20 years) with cerebral palsy were analyzed. All patients had neuromotor disease and 18 children had spastic diplegia or quadriplegia. All patients could initiate voluntary knee extension but lacked full passive extension. Five patients (10 knees) were free walkers with a mean motor severity index of 19 and mean fixed knee contracture of 20 degrees. Fifteen patients (29 knees) were not free walkers and 13 were wheelchair ambulators. They had a mean motor severity index of 8 and mean fixed knee contractures of 30 degrees. Surgical procedures included various combinations of hamstring lengthening and/or posterior capsulotomy to allow free passive knee extension, with or without quadriceps mechanism shortening, to enhance voluntary extension. The best results were in patients who had hamstring lengthening, posterior capsulotomy, and quadriceps mechanism shortening.     

Force of femoral abductors in patients with lumbar nucleus pulposus prolapse]

In 50 patients with lumbar nucleus pulposus prolapse the force of femoral abductors was determined by the test of Lovett and by means of dynamometric measurements. In 90% of patients paresis of these muscles was found. A comparison of the incidence of other signs of nerve root damage such as paresis of plantar and dorsal flexion of the foot and toes, sensory impairment on the foot and lack or weakness of ankle jerk showed that paresis of fermoral abductors was most frequent among them. This fact is explained by a particular predisposition for development of uncleus pulposus prolapse at the level of 4th and 5th intervertebral discs with resulting injury to the nerve roots L4, L5, and S1 innervating femoral abductors. The authors think that paresis of femoral abductors may be a pathognomonic sign in the diagnosis of nerve root lesions caused by nucleus prolapse at the levels L4-L5 or L5-S1. The frequency of paresis and the degree of weakness indicate the necessity of motor rehabilitation of this music group in comprehensive treatment of patients with lumbar disc prolapse.     

Étude comparative de l’évaluation clinique de l’angle poplité en décubitus dorsal versus décubitus latéral asymétrique,chez des sujets infirmes moteurs cérébraux et polyhandicapés (paralysés cérébraux)

Clinical assessment of lengthening possibilities of hamstring muscles is of great importance for cerebral palsied patients because of progressive and early diminution and its functional and orthopaedic consequences. Traditionally, a clinical assessment is carried out by measuring the popliteal angle with the patient in supine position and hip flexed at 90°. Nevertheless, for patients with CP, able to understand orders, popliteal angle data can change from one clinician to the other because of varying resistance of the muscles at lengthening. On the other hand, more patients relax spontaneously when lying in a lateral and asymmetrical position with the lower limb examined flexed, than in a supine position. In the case where the relaxed state is insufficient, we can use a specific maneuver in order to relax him more. The aim of this article is to report the results of a study made to compare popliteal angle in supine position versus lateral and asymmetrical position. Throughout the maneuvers, the degrees of contraction of the muscles were recorded by a surface electromyography. Variations of the angles were measured with electrical goniometers and verified, on obtaining the final popliteal angle by a mechanical goniometer. Data obtained at the end of the study with a group of 12 patients from 8 to 15 years old, showed that for all patients the angle is higher in the lateral and asymmetrical position than in the supine position, that is to say between 20° to 40° more. These results contest the choice of the decubitus dorsal position to assess the popliteal angle allowed by intrinsic lengthening possibilities (visco-elasticity) of the hamstring muscles and not active resistances due to muscular contraction from diverse pathological factors.     

The Rate of Wallerian Degeneration in Cultured Neurons from Wild Type and C57BL/WldS Mice Depends on Time in Culture and may be Extended in the Presence of Elevated K+ Levels

Wallerian degeneration of severed axons is delayed in C57BL/Wld^s mice. We have examined this further in cultured sympathetic, sensory and CNS neurons using superior cervical ganglion (SCG), dorsal root ganglion (DRG) and cerebellar granule neurons respectively from neonatal mice. We found that the time taken for the neurites to degenerate depends upon the length of time in culture before cutting, reaching a maximum by -7 days when C57BL/Wld^S neurites survive for >6 days after axotomy. The onset of degeneration could also be extended in SCG and DRG neurites from wild type C57BL/6J mice. After 7 days in culture these neurites normally degenerate within -12–16 h of axotomy, but in the presence of raised K⁺ (50 mM) degeneration often did not begin until a further 2 days had lapsed. Under similar conditions degeneration of neurites from C57BL/Wld^S mice was also found to be further delayed, extending survival from -5–6 days to >7 days. The L-type Ca²⁺ channel blockers nifedipine (5 μM) and verapamil (10 μM) both blocked the effect of raised [K⁺], although not completely. Thapsigargin, which raises cytoplasmic [Ca²⁺], and the cAMP analogue 8-(4-chlorophenylthio)cAMP were also able to delay degeneration, but only when added 24 h prior to axotomy. These results show that it is possible to influence the course of Wallerian degeneration and that increases in levels of cytoplasmic Ca²⁺ can protect neurites from its onset.     

Plantar Flexion with Noxious Dorsal Foot Stimulation in Brain Death

Background

Plantar flexion with plantar stimulation has been well described in brain death, and is compatible with brain death. However, plantar flexion with stimulation to the dorsal surface of the foot has not been reported previously in brain dead patients.

Methods

Case report with Technetium-99?m hexamethylpropyleneamine oxime brain scan and video.

Results

A 46-year-old woman suffered severe anoxic brain injury following massive pulmonary embolism 5?days after arthroscopic knee surgery. Neurologic examination was consistent with brain death, with the exception of plantar flexion when noxious stimulation was applied to the dorsal surface of the great toe on each side. Ancillary testing with a technetium-99?m nuclear scan demonstrated absence of cerebral perfusion, supporting the diagnosis of brain death.

Conclusions

Noxious stimulation to the dorsal surface of the foot may trigger spinally mediated plantar flexion in patients with brain death.     

The Effect of Barium on [3H]Noradrenalin Release from the Human Neuroblastoma SH-SY5Y

Replacement of Ca²⁺ with Ba²⁺ in HEPES-buffered saline stimulated [³H]noradrenalin release in the human neuroblastoma clone SH-SY5Y by up to 20% of the cell content in the absence of other secretory stimuli. The Ba²⁺-evoked release was inhibited by 85% by 3 μM tetrodotoxin and 95% by 5 μM nifedipine. Ba²⁺ also increased the potency of K⁺-evoked release of [³H]noradrenalin, as maximal release was observed with 60 mM K⁺ compared with the 100 mM K⁺ necessary to achieve maximal release in the presence of Ca²⁺. In contrast, replacing Ca²⁺ with Ba²⁺ had little effect on carbachol- and bradykinin-evoked release of [³H]noradrenalin. No evidence was obtained from studies on changes in [Ca²⁺]_i (in response to 100 pM carbachol) using fura-2 that Ba²⁺ could enter intracellular stores in SH-SY5Y cells. Whole-cell patch-clamp studies showed that Ba²⁺ depolarizes SH-SY5Y cells as well as enhancing inward Ca²⁺ channel currents and shifting their voltage dependence to more negative values. These results are discussed in terms of the hypothesis that Ba²⁺ blocks K⁺ channels, leading to depolarization followed by opening of voltage-sensitive Na⁺ channels. This in turn opens voltage-sensitive L-type Ca²⁺ channels, which are coupled to the release of [³H]noradrenalin in SH-SY5Y cells.