Amino acid transmitters in the mammalian central nervous system

Amino Acid Transmitters in the Mammalian Central Nervous System 159
tant to strychnine and to bicuculline (RYALL, PIERCEY and POLOSA, 1972; CURTIS,
GAME and MCCULLOCH, unpublished observations). Although an explanation
has been offered in terms of the presence on Renshaw cells of strychnine-insensitive
glycine receptors which would be compatible with all Renshaw cells being glycinergic
(RYALL et al., 1972), the finding that tetanus toxin abolishes the inhibition of
Renshaw cells by hind limb impulses, but does not modify "mutual" inhibition,
(CURTIS, GAME, and MCCULLOCH, unpublished observations) tends to exclude
glycine (and GABA) as an inhibitory transmitter for this process. Further investigation
of both "mutual" inhibition and the pause seems warranted, particularly
as hyperpolarizing IPSP's have not been demonstrated for either phenomenon.
The effects of tetanus toxin on spinal inhibition are relevant to transmitter
functions of both glycine and GABA. With respect to glycine, spinal inhibitions
sensitive to strychnine are also reduced by tetanus toxin (Cat: BROOKS, CURTIS
and ECCLES, 1957; CURTIS and DE GROAT, 1968). However, unlike the situation
after strychnine, spinal neurones retain sensitivity to glycine (CURTIS and DE
GROAT, 1968; GUSHCHIN, KOZHECHKIN and SVERDLOV, 1969). Since the levels
of glycine within the cord are little influenced (Cat: JOHNSTON, DE GROAT, and
CURTIS, 1969; FEDINEC and SHANK, 1971; see also SEMBA and KANO, 1969),
tetanus toxin apparently interferes with the release of this amino acid from inhibitory
terminals.
4.12.3.2 GABA
The depression of the firing of spinal interneurones, parasympathetic preganglionic
neurones, motoneurones and Renshaw cells by electrophoretic GABA
(Cat: CURTIS et al., 1959; DE GROAT, 1970. Rat: BISCOE et al., 1972) is associated
with an increased membrane potential and a conductance increase similar to
that induced by glycine (CURTIS et al., 1968b). This, together with the effects
of intrathecal and systemic GABA on spinal reflexes (KuNo and MUNEOKA,
1962 ; BHARGAVA and SRIVASTAVA, 1964 ; DHAWAN et al., 1972), and the intraspinal
distribution of the amino acid, suggests that GABA is an inhibitory transmitter
in the cord. Furthermore, the relative insensitivity of depression of spinal neurone
firing by GABA to strychnine (CURTIS et al., 1968a, b; DE GROAT, 1970; LARSON,
1969; CURTIS et al., 1971c; BlSCOE et al., 1972), and the antagonism of the
postsynaptic effects of GABA by bicuculline (CURTIS et al., 1971a; B1sco~
et al., 1972), related alkaloids (JOHNSTON et .al., 1972), and penicillin (DAVI-
DOFF, 1972C; CURTIS et al., 1972b), indicate that GABA is unlikely to be the
transmitter of inhibitions suppressed by strychnine and strychnine-like glycine
antagonists.
Consideration of the transmitter role of GABA in the spinal cord is closely
related to the controversial subject of" presynaptic" inhibition, a process reviewed
recently in depth (ScHt~IDT, 1971). Although there is general agreement that
this type of inhibition is of longer latency and duration than that discussed
in the previous section, and is insensitive to strychnine but reduced by picrotoxinin
and bicuculline, there is still debate regarding the mechanism of the process.
The inhibition has been measured by the reduction in amplitude of either intracellularly
recorded EPSP's or monosynaptic reflexes, and is diminished by picrotoxin