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G A Kerkut

Publications and source records attributed to G A Kerkut.

At least 19 recordsLinked to original sources

The effect of bicuculline and baclofen on the dorsal root-ventral root reflex in the isolated spinal cord.

1. In the lumbar spinal cord, 10(-6) M bicuculline reduces the inhibition of the dorsal root-ventral root (DR-VR) reflex produced by lateral stimulation of the spinal cord. The inhibition returns on washing in control artificial cerebrospinal fluid (ACSF). 2. Baclofen (10(-6) M) inhibits the monosynaptic DR-VR reflex which returns on washing in control ACSF. 3. This suggests an involvement of GABAA receptors in the lateral inhibition and GABAB receptors in the DR-VR reflex system. 4. The increased activity seen following bicuculline or tubocurarine probably resets the "set point" of neural activity to a lower level.

Action Potentials

Tubocurarine and strychnine block Renshaw cell inhibition in the isolated mammalian spinal cord.

1. Stimulating a lumbar dorsal root (A) of an isolated mammalian spinal cord preparation sets up a reflex (DR-VR) in the corresponding ventral root (A) of that segment. 2. If an adjacent motor root (B) is antidromically stimulated 100 msec before the dorsal root A is stimulated, it inhibits the ventral root A response. (i.e. Renshaw cell inhibition of A through antidromic stimulation of recurrent collateral of B). 3. Stimulation of the lateral side of the spinal cord 5 mm rostral to the DR-VR reflex sets up a powerful inhibition of the reflex. 4. The inhibition is abolished by tubocurarine, or by strychnine indicating that the lateral stimulation is activating a cholinergic and a glycinergic pathway. 5. Addition of tubocurarine increases the steady "spontaneous" activity in the motor roots. 6. Addition of tubocurarine and 10(-3) M magnesium produces long lasting rhythmic bursting activity in the motor roots that persists even after 45 min of washing. 7. The isolated mammalian spinal cord preparation in addition to having active sensory, motor, and interneurones, has active Renshaw cells that can be studied using this preparation free from any blood-brain barrier and so are easily permeated by tubocurarine, etc.

Action Potentials

Differential sensitivity of dorsal and ventral root activity to magnesium and 2-amino-5-phosphonovalerate (APV) in an isolated mammalian spinal cord preparation.

Spontaneous activity emerging from the isolated hamster spinal cord simultaneously along the ventral and dorsal lumbar roots was shown by inter-spike interval analysis to have different firing patterns. Ventral root firing was reduced in solutions containing 1 mM magnesium or sub-micromolar concentrations of 2-amino-5-phosphonovalerate (APV), whereas the activity in the dorsal roots was unchanged. Differences in sensitivity to magnesium and APV were also shown on the evoked ventral and dorsal root reflexes, with the dorsal root reflex being unaffected, and the ventral root reflex exhibiting a long latency component that was sensitive to magnesium and APV. These results indicate that NMDA receptors are involved in the generation of part of the ventral root responses in the spinal cord, but not in the generation of the dorsal root reflex and spontaneous dorsal root activity.

2-Amino-5-phosphonovalerate

Studying the isolated central nervous system; a report on 35 years: more inquisitive than acquisitive.

1. The CNS from invertebrate animals such as slugs, snails, leeches, and cockroaches, can be isolated and kept alive for many hours. 2. The electrical and pharmacological properties of invertebrate CNS neurons have many similarities and it is probable that the basic rules governing the CNS evolved more than 600 million years ago. 3. The nerve cells can show sodium action potentials, calcium action potentials, EPSP, IPSP, biphasic potentials, electrogenic sodium pump potentials, and a variety of potassium, sodium, calcium and chloride currents. 4. Invertebrate CNS ganglia contain identifiable individual nerve cells whose properties and responses to neurotransmitters and drugs are constant and repeatable from preparation to preparation. 5. It was possible to set up an isolated CNS-nerve trunk-muscle preparation and study the transport of radioactive material from the CNS to the muscle and from muscle to CNS. This has provided information about axoplasmic transport in both invertebrate and vertebrate preparations. 6. The methods developed from studies of invertebrate isolated CNS preparations have been applied to vertebrate isolated CNS preparations. 7. In addition to thin slices of the mammalian brain, it is possible to keep 5 cm lengths of the whole mammalian spinal cord and brain stem alive for many hours. 8. The isolated mammalian spinal cord has functional ipsilateral and contralateral reflexes, ascending and descending pathways, extensive sensory integrative local area networks, and inhibitory interneuron circuits. Much of the in vivo circuitry is functional in vitro. 9. The isolated mammalian spinal cord and brain stem can be developed to include functional higher brain circuits that will provide increased understanding of the control and integrative action of the mammalian central nervous system.

Animals

The dorsal root reflex in isolated mammalian spinal cord.

1. The dorsal root reflex has been investigated in an isolated preparation of adult mammalian spinal cord. 2. Both evoked and spontaneous activity can be recorded from the cord in the dorsal spinal roots. 3. The spontaneous activity has a characteristic pattern of firing in bursts of action potentials. Spontaneous and evoked activity are optimum at temperatures between 25 and 27 degrees C; little activity can be detected above 35 degrees C. 4. The spontaneous dorsal root activity has been shown to be correlated with negative potentials in the dorsal horn of the cord, and intracellular recordings made from primary afferent fibres have shown spontaneous primary afferent depolarizations (PAD) which underlie the generation of the spontaneous dorsal root activity. 5. The evoked dorsal root reflex has been shown to spread up to 16 spinal segments both rostrally and caudally from the stimulated dorsal root, and to the contralateral side of the cord. 6. The spontaneous dorsal root activity in widely separated segments has been shown by cross-correlation analysis to be linked both ipsi- and contra-laterally. 7. The significance of such a widespread system for the generation of PAD is discussed.

Afferent Pathways

The effect of diaminopyridines on the activity recorded in the dorsal roots of isolated spinal cord.

1. The diaminopyridines (DAP) increase the activity recorded in the dorsal roots of an isolated hamster spinal cord preparation. 2. The threshold for 3,4 DAP was 3 x 10(-6) M and the maximum effect was 10(-4) M. The threshold for 2,3 DAP was 3 x 10(-4) M and the maximum effect was at 10(-3) M. The threshold for 2,6 DAP was 10(-4) M and its maximum effect was at 3 x 10(-2) M. 3. When compared with the monoamino pyridines (AP) 4 AP was the most effective and the order of potency was 4 AP greater than 3,4 DAP greater than 2,3 DAP greater than 2 AP = 3 AP greater than 2,6 DAP. 4. Treatment with AP increased the activity simultaneously recorded in the dorsal and ventral roots, but whilst that in the dorsal root continued after washing away the amino pyridine, that in the ventral root ceased for a period of time. 5. There are indications that the amino pyridines may differently affect dorsal and ventral interneurones.

Aminopyridines