Microelectrode studies in the frog isolated spinal cord during depression by general anaesthetic agents

Abstract

. Extracellular and intracellular potentials have been recorded from the isolated spinal cord of the frog during depression of synaptic transmission by volatile and barbiturate general anaesthetic agents. . Volatile agents did not impair conduction in presynaptic terminals in concentrations which completely blocked synaptic transmission. . Methohexitone consistently impaired conduction in presynaptic terminals long before transmission through polysynaptic pathways was blocked. . Volatile agents depressed the excitability of the motoneurone membrane, as evidenced by impaired antidromic invasion, reduced excitability to direct stimulation, depression of the synaptic potential and elevation of firing threshold. It is concluded that these actions are responsible for the depressant effect of volatile agents on spinal reflexes. . Methohexitone produced an increase in the excitability of the motoneurone membrane, as evidenced by enhanced antidromic invasion, increased excitability to direct stimulation and potentiation of short latency responses. Despite this excitatory action, the polysynaptic pathways through the cord were depressed by an action of the drug on conduction in presynaptic terminals. . It is suggested that the sensitivity of the motoneurone membrane to volatile agents may contribute to the good muscle relaxant properties of these drugs in clinical use.

Presynaptic action of barbiturates in the frog spinal cord.

“…The available evidence suggests that the barbiturates act mainly at synapses, suppressing excitatory synaptic transmission (1)(2)(3)(4)(5)(6)(7)(8) and usually either preserving or augmenting inhibitory synaptic transmission (6,(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The action of barbiturates on the spinal monosynaptic pathway has received the most rigorous analysis, and it has been shown that, in low doses, they reduce the amount of transmitter released from the primary afferents (4 The pH of the drug solutions was adjusted when necessary with NaOH or HCl.…”

The Pharmacology of Sedative/Hypnotics, Alcohol, and Anesthetics: Sites and Mechanisms of Action

“…Thus, with urethane and ethanol as well as other short chain alcohols, the synaptic transmission was not more sensitive than axonal conduction, clearly indicating rather marked differences in selectivity of action among this group of general depressants. (Some of the reports are: BROOKS and ECCLES, 1947;SHAPOVALOV, 1963;CRAWFORD and CURTIS, 1966;SOMJEN and GILL, 1963;SOMJEN, 1963;SOMJEN et aI., 1965;THESLEFF, 1956;CRAWFORD, 1970;WESTMORELAND et aI., 1971;RICHARDS, 1971RICHARDS, , 1972aRICHARDS, , b, 1973RICHARDS, , 1974RICHARDS et aI., 1975;NICOLL, 1972NICOLL, , 1974NICOLL, , 1975aRICHENS, 1969;THOMSON and TURKANIS, 1973;GALINDO, 1969GALINDO, , 1972DEJONG et aI., 1970;ADAMS et aI., 1970;ADAMS, 1974;BARKER, 1975;BARKER and GAINER, 1973;BARKER and NICOLL, 1973;RANSOM and BARKER, 1975;WEAKLY, 1969;SCHLOSSER, 1971;GAGE, 1965;GAGE et aI., 1975;QUILLIAM, 1959;ZORYCHTA, 1974;KLEE, 1976, 1977. ) …”

“…ZORYCHTA'S data are consistent with an action of the anesthetics resulting in either an increased level of existing presynaptic inhibition or altering more directly the transmitter release mechanism. It is, however, very difficult to delimit the degree to which the variable depression of electrical excitability of the postsynaptic neuron is significant to transmission block (SOMJEN, 1967;ZORYCHTA, 1974;RICHENS, 1969;EIDELBERG and WOOLEY, 1970;SHAPOVALOV, 1963). NICOLL (1975a, b) has recently extended the understanding of anesthetics using the frog spinal cord preparation to demonstrate that barbiturates either mimic or potentiate the action of the transmitter from the interneuron whose axon terminates on the presynaptic ending.…”