SELECTIVE ACTION OF ANESTHETICS ON SYNAPSES AND AXONS IN MAMMALIAN SYMPATHETIC GANGLIA

Abstract

The concns. of various anesthetics and other substances required to block synaptic excitation of sympathetic ganglion cells were compared with concns. required to block conduction along sympathetic nerve fibers. Observations were made on perfused stellate ganglia, excised thoracic and cervical sympathetic nerves, and excised vagus nerves of cats, and on excised superior cervical sympathetic trunks of rats and rabbits. Impulses were initiated by supramaximal electric stimuli and the resultant action potentials recorded. Chloretone, chloroform, ether, and Na pentobarbital depressed synaptic transmission in concns. similar to those known or assumed to exist in the blood during surgical anesthesia, while ethyl alcohol and urethane required higher concns. There were no important differences between concns. required to block conduction along autonomic nerve fibers of different types (A, B and C). This was observed with chloretone, chloroform, ether, pentobarbital, and ethyl alcohol. Synaptic transmission was depressed more readily than conduction along any type of axon by each of these agents, and by cocaine, amyl alcohol and hexyl alcohol, but not by urethane or by methyl, ethyl, propyl, or butyl alcohols. Selective action of pentobarbital was accentuated during repetitive activity. Transient facilitation of synaptic excitation was observed with certain concns. of methyl and ethyl alcohols. Degree of selective action was measured quantitively by the ratio of the concn. required to halve the height of action potential of impulses conducted along a nerve trunk to the concn. required to halve the height of the postsynaptic action potential. Selective action on synaptic processes was thus found to increase systematically as the C-atom chain was lengthened in alcohols, and tended to increase with mol. wt. of most substances studied. The selective action never exceeded a factor of about 10 (observed with pentobarbital) for any anesthetic or alcohol, although it could be much greater for other pharmacological agents, such as nicotine. Molar concns. for given degree of block of either synaptic transmission or axonal conduction decreased systematically with increase in mol. wt. among the alcohols and similarly tended to decrease with mol. wt. among most of the substances investigated. The thermodynamic activities required for given effect differed very much less than molar concn., at least among alcohols, ether, and chloroform. Thus, selective action may result either from a specific effect of an anesthetic on synaptic processes or from the relatively small "factor-of-safety" in trans-synaptic excitation compared to axonal conduction.