Neuropharmacological and neurophysiological consequences of the co-release of neurotransmitters

Abstract

When two or more transmitters are liberated at different synapses on the same neurone and the sites of action are restricted to the immediately adjacent subsynaptic membrane, they may mutually interact as a consequence of their postsynaptic effects. Depolarisations arising from selective conductance increases at different parts of the neurone may be synergistic at the sites of impulse generation, although the summation may be less than additive if the sites of origin of the depolarising effects are so close together that an increase conductance, at one synapse, short-circuits the depolarising currents produced at other synapses. Similarly, the conductance shunts and hyperpolarisations produced by inhibitory neurotransmitters may reduce excitatory potentials to levels at which the threshold for impulse initiation is not reached. Excitatory and, presumably, inhibitory transmission may also be attenuated by presynaptic inhibition in which axo-axonic synapses liberate transmitters which reduce the output of transmitter from the primary afferent and possibly higher order fibres. Such may be considered to be the classical mechanisms of synaptic transmission in which the effects of one transmitter modulates the action of another but each retains an independence with respect to neuronal pathways, control of release and independent sites of action on the postsynaptic neurone.