Abstract
The action of Co2+ on the isolated frog spinal cord was studied by extracellular application of the ion in the superfusing solution. A complete and reversible blockade of chemical synaptic transmission by Co2+ (3 mmol/l) could be achieved after a superfusion period of 20–30 min. During continued Co2+ application (>60 min) the following effects upon the motoneuron membrane, dorsal root and ventral root fibres were observed.
Motoneurons and ventral root fibres:
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1.
prolongation of initial segment action potential to a maximum of 30 ms,
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2.
blockade of the long afterhyperpolarization,
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3.
abolition of adaptation,
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4.
increased duration of fibre action potential in the ventral root,
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5.
backfiring after ventral root stimulation.
Dorsal root fibres:
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1.
prolongation of the extraspinal fibre action potential,
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2.
marked prolongation of the action potential of the terminal region,
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3.
backfiring of multiple action potentials after dorsal root stimulation.
Even in the presence of Co2+, when synaptic transmission was completely blocked, strong convulsive reactions of the isolated spinal cord were observed. Intracellular injection of Co2+ into motoneurons did not affect the action potential, but led to a shift of the EIPSP towards the membrane potential.
The results indicate that the induction of convulsive reactions by Co2+ is mainly due to a prolongation of action potentials. The plateau-like deformation of the action potential of the initial segment membrane and presumably of the terminal region of nerve endings results in retrograde propagation of action potentials and in some cases induces oscillatory discharge of single neurons.
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References
Alvarez-Leefmans FJ, De Santis A, Miledi R (1979) Effects of some divalent cations on synaptic transmission in frog spinal neurons. J Physiol 294:387–406
Araki T, Terzuolo CA (1962) Membrane currents in spinal motoneurons associated with the action potential and synaptiactivity. J Neurophysiol 25:772–789
Ayala GF, Dichter M, Gumnit RJ, Matsumoto H, Spencer WA (1973) Genesis of epileptic interictal spikes: New knowledge of cortical feedback systems suggests a neurophysiological explanation of brief paroxysms. Brain Res 52:1–17
Baker PF, Meves H, Ridgway EB (1973) Effects of manganese and other agents on the calcium uptake that follows depolarization. J Physiol 231:511–526
Baldissera G, Gustafsson B (1971) Regulation of repetitive firing in neurons by afterhyperpolarization conductance. Brain Res 30:431–434
Barrett EF, Barrett JN (1976) Seperation of two voltage sensitive potassium currents and demonstration of a tetrodotoxin-resistance calcium current in frog motoneurons. J Physiol (Lond) 255:737–774
Barrett JN, Crill WE (1974) Specific membrane properties of cat motoneurons. J Physiol (Lond) 239:301–324
Barron DH, Mathews BHC (1938) The interpretation of potential changes in the spinal cord. J Physiol 92:276–321
Blaustein MP (1975) Effects of potassium, veratridine and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro. J Physiol 247:617–655
Bruggencate G ten, Lux HD, Liebl L (1974) Possible relationship between extracellular potassium activity and presynaptic inhibition in the spinal cord of the cat. Pflügers Arch ges Physiol 349:301–317
Buehrle Ch-Ph, Sonnhof U (1979) The ionic mechanism of the IPSP in frog spinal motoneuron. Pflügers Arch Suppl 382
Butler AB, Willmore LJ, Fuller PM, Bass NH (1977) Cytochemical affinity of pyramidal cell dendrites for divalent cobalt during initiation and calcium induced blockade of epileptiform discharge. Experimental Neurol 56:386–399
Coombs JS, Eccles JC, Fatt P (1955a) The electrical properties of motoneurone membrane. J Physiol (Lond) 130:291–325
Coombs JS, Curtis DR, Eccles JC (1957) The interpretation of spike potentials of motoneurons. J Physiol 139:198–231
Courtois A (1972) Motor phenomenology of cobalt experimental epileptic focus in motor cortex of cat during various stages of vigilance. Electroencephalo Clin Neurophysiol 32:259–267
Craig CR, Hartmann ER (1973) Concentration of amino acids in the brain of cobalt epileptic rats. Epilepsia (Amst) 14:409–414
Dambach GE, Erulkar SD (1973) The action of calcium at spinal neurones of the frog. J Physiol (Lond) 228:799–817
Del Castillo J, Katz B (1954) The effect of magnesium of the activity of motor nerve endings. J Physiol (Lond) 124:553–559
Dewar AG, Dow RC, McQueen JK (1972) RNA and protein metabolism in cobalt induced lesions in rat brain. Epilepsia (Amst) 13:552–560
Dodge FA Jr, Rahamimoff R (1962) Co-operative action of calcium ions in transmitter release at the neuromuscular junction. J Physiol (Lond) 193:419–432
Dow RS, Fernandez-Guardiola A, Manni E (1962) The production of cobalt experimental epilepsy in the rat. Electroenceph Clin Neurophysiol 14:399–407
Eccles JC (1961) The mechanism of synaptic transmission. Erg Physiol 51:299–430
Eccles JC, Malcolm JL (1946) Dorsal root potentials of the spinal cord. J Neurophysiol 9:139–160
Emson PC (1975) Metal implants as a model for epilepsy. Biochem Neurol
Emson PC, Joseph MH (1975) Neurochemical and morphological cobalt-induced epilepsy in the rat. Brain Res 93:91–110
Fatt P (1957) Electric potentials occuring around a neuron during its antidromic invasion. J Neurophysiol 20:27–60
Feng TB (1936) Studies on the neuromuscular junction. II. The universal antagonism between calcium and curarizing agencies. Chin J Physiol 10:513–528
Grinnell AD (1966) A study of the interaction between motoneurones in the frog spinal cord. J Physiol 182:612–648
Hackett JT (1976) Selective antagonism of frog cerebellar synaptic transmission by manganese and cobalt ions. Brain Res 114:47–52
Hartmann ER, Colasanti BK, Craig CR (1974) Epileptogenic properties of cobalt and related metals applied directly to cerebral cortex of rat. Epilepsia 15:121–129
Hoover DB, Graig CR, Colasanti BK (1977) Cholinergic involvement in cobalt-induced Epilepsy in the rat. Exp Brain Res 9:501–513
Jansen JKS, Nicholls JG (1973) Conductance changes an electrogenic pump and the hyperpolarization of leech neurones following impulses. J Physiol 229:635–655
Katz B, Miledi R (1963) A study of spontaneous miniature potentials in spinal motoneurones. J Physiol 168:389–422
Koketsu K (1956) Intracellular slow potential of dorsal root fibers. Am J Physiol 184:338–344
Koyama HH (1972) Amino acids in the cobalt induced epileptogenic cat's cortex. Canad J Physiol Pharmacol 50:740–752
Kriz N, Syková E, Vyklický L (1975) Extracellular potassium changes in the spinal cord of the cat and their relation to slow potentials, active transport and impulse transmission. J Physiol (Lond) 238:167–182
Krnjevic K, Morris ME (1974) Extracellular accumulation of K+ envolved by activity of primary afferent fibers in the cuneate nucleaus and dorsal horn of cats. Canad J Physiol Pharmacol 52:852–871
Krnjevic K, Morris ME (1975) Correlation between extracellular focal potentials and K+ potentials evoked by primary afferent activity. Can J Physiol Pharmacol 53:912–922
Llinas R, Steinberg IZ, Walton K (1976) Presynaptic calcium currents and their relation to synaptic transmission voltage clamp study in squid giant synapse and theoretical model for the calcium gate. Proc Natl Acad Sci 17:2918–2923
Lothman EW, Somjen GG (1975) Extracellular potassium activity intracellular and extracellular potential responses in the spinal cord. J Physiol (Lond) 252:115–136
Lunt G, Grove Y (1975) The effects of cobalt-induced epilepsy on the unesterified fatty acid content in the rat cerebral cortex. Biochemical Soc. Transactions 557th Meeting, vol 3, 701–702
Magherini PC, Precht W, Schwindt PC (1976) Electrical properties of frog motoneurons in the in situ spinal cord. J Neurophysiol 39:459–475
Matsumoto H (1964) Intracellular events during activation of cortical epileptiform discharges. Electroencephalogr Clin Neurophysiol 17:294–307
Meech RW (1972) Intracellular calcium injection causes increased potassium conductance in Aplysia nerve cells. Comp Biochem Physiol 42A:493–499
Meech RW (1974) The sensitivity of the Helix aspersa neurones to injected calcium ions. J Physiol 237:259–277
Meech RW, Standen NV (1975) Potassium activation in Helix aspersa neurones under voltage clamp: a component mediated by Ca influx. J Physiol 249:211–239
Noebels JL, Prince DA (1977) Presynaptic origin of penicilin afterdischarges at mammalian nerve terminals. Brain Res 138:59–74
Osorio I, Hackman JC, Davidoff RA (1979) GABA or potassium: which mediates primary afferent depolarization? Brain Res 161:183–186
Prince DA (1978) Neurophysiology of Epilepsy. Ann Rev Neuroscience 1:395–415
Rubin RP (1970) The role of calcium in the release of neurotransmitter substances and hormones. Pharmacol Rev 22:389–417
Schmidt RF (1971) Presynaptic inhibition in the vertebrate central nervous system. Ergebn Physiol 63:21–101
Schwarzkroin PA, Mutani R, Prince DA (1975) Orthodromic and antidromic effects of a cortical epileptiform focus on ventrolateral nucleus of the cat. J Neurophysiol 38:795–811
Shapovalov AJ, Shiriaev BI (1978) Electrical coupling between primary afferents and amphibian motoneurons. Exp Brain Res 33:299–312
Shapovalov AJ, Shiriaev BI (1980) Dual mode of junctional transmission at synapses between single primary afferent fibres and motoneurones in the amphibian. J Physiol 306:1–15
Shibuya M, Fariello R, Farley IJ, Price KS, Lloyd KG, Hornykiewicz O (1978) Cobalt injections into the substantia nigra of the rat: Effects of behaviour and dopamine metabolism in the stratum. Exp Neurol 58:486–499
Sonnhof U, Richter DW, Taugner R (1977) Electrotonic coupling between frog spinal motoneurons. An electrophysiological and morphological study. Brain Res 138:197–215
Sonnhof U, Bührle Ch-Ph (1980) An analysis of glutamate-induced ion fluxes across the membrane of spinal motoneurons of the frog. Adv Biochem Psychopharmacol 27:195–204
Syková E, Shiriaev B, Kriz N, Vyklický L (1976) Accumulation of extracellular potassium in the spinal cord of frogs. Brain Res 106:413–417
Sypert G, Bidgood D (1977) Effect of intracellular cobalt ions on postsynaptic inhibition in cat spinal motoneurons. Brain Res 134:372–376
Taugner R, Sonnhof U, Richter DW, Schiller A (1978) Mixed (chemical and electrical) synapses on frog spinal motoneurons. Cell Tiss Res 193:41–59
Van Gelder NM (1972) Antagonism by taurine of cobalt induced epilepsy in cat and mouse. Brain Res 47:157–162
Voss Ch, Schiller A, Taugner R (1980) Morphology and distribution of the synapses to the spinal motoneuron of the frog. With the special reference to the subsurface cisterns. Cell and Tiss Res 213:253–271
Ward AA (1961) Epilepsy. Int Rev Neurobiol 3:137
Ward AA (1969) The epileptic neuron: Chronic foci in animals and man. In: Jasper HH, Ward AA, Pope A (eds) From basic mechanism of epilepsies. Little Brown and Co., Boston, pp 263–293
Washizu Y (1960) Single spinal motoneurons excitable from two different antidromic pathways. Jpn J Physiol 10:121–131
Weakly JN (1973) The action of cobalt ions on neuromuscular transmission in the frog. J Physiol (Lond) 234:597–612
Willmore LY, Fuller PM, Butler AB, Bass NH (1975) Neuronal compartmentation of ionic cobalt in rat cerebral cortex during initiation of epileptoform activity. Exp Neurol 47:280–289
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Buchert-Rau, B., Sonnhof, U. An analysis of the epileptogenic potency of CO2+-its ability to induce acute convulsive activity in the isolated frog spinal cord. Pflugers Arch. 394, 1–11 (1982). https://doi.org/10.1007/BF01108300
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DOI: https://doi.org/10.1007/BF01108300