The released neurotransmitter molecules bind to the extracellular part of postsynaptic membrane receptors called transmitter-gated channels. Binding of neurotransmitter induces a conformational change in these channel proteins that causes its pore to open. The response that is ultimately generated depends on the identity of the ion that enters the cell. For instance, influx of Na causes local depolarization in the postsynaptic membrane, which under favorable conditions (sufficient amount and duration of neurotransmitter release) prompts the opening of voltage-gated Na channels, thereby generating a nerve impulse.
Some amino acid and amine neurotransmitters may bind to G-protein–coupled receptors to produce longer-lasting and more diverse postsynaptic responses. The neurotransmitter binds to a transmembrane receptor protein on the postsynaptic membrane. Receptor binding activates G-proteins, which move along the intracellular surface of the postsynaptic membrane and eventually activate effector proteins. These effector proteins may include transmembrane G-protein–gated ion channels or enzymes that synthesize second-messenger molecules (page 335). Several neurotransmitters (i.e., acetylcholine) can generate different postsynaptic actions, depending on which receptor system they act (see below).
Porocytosis describes the secretion of neurotransmitter that does not involve the fusion of synaptic vesicles with the presynaptic membrane.
Based on evaluation of physiologic data and the structural organization of nerve synapses, an alternate model of neurotransmitter secretion called porocytosis has recently been proposed to explain the regulated release of neurotransmitters. In this model, secretion from the vesicles occurs without fusion of the vesicle membrane with the presynaptic membrane. Instead, the synaptic vesicle is anchored to the presynaptic membrane next to Ca2-selective channels by SNARE and synaptotagmin proteins. In the presence of Ca2, the vesicle and presynaptic membranes are reorganized to create a 1-nm transient pore connecting the lumen of the vesicle with the synaptic cleft. Neurotransmitters can then be released in a controlled fashion through these transient membrane pores (see Fig. 12.7).
The chemical nature of the neurotransmitter determines the type of response at that synapse in the generation of neuronal impulses.
The release of neurotransmitter by the presynaptic component can cause either excitation or inhibition at the postsynaptic membrane.
 In excitatory synapses, release of neurotransmitters such as acetylcholine, glutamine, or serotonin opens channels), prompting an influx of Na that causes local reversal of voltage of the postsynaptic membrane to a threshold level (depolarization). This leads to initiation of an action potential and generation of a nerve impulse.
 In inhibitory synapses, release of neurotransmitters such as -aminobutyric acid (GABA) or glycine opens transmitter-gated Cl channels (or other anion channels), causing Cl– to enter the cell and hyperpolarize the postsynaptic membrane, making it even more negative. In these synapses, the generation of an action potential then becomes more difficult.