Receptors for peptides, like biogenic amines, are mostly of the metabotropic type and are linked to G proteins, which transmit effects through second messenger cascades. Interestingly, studies consistently show a discrepancy between the locations of terminals containing a specific peptide and the receptors for that peptide. Consequently, these receptors are often activated by neurotransmitter diffusing through the extracellular space rather than at synapses. This implies that these receptors are highly sensitive to their agonists, as they are exposed to much lower concentrations of the agonist.
In contrast to other neurotransmitters, NO and CO do not bind to receptors. However, they do affect cell activity by activating enzymes involved in second messenger cascades, such as guanylyl cyclase. Additionally, NO has the ability to modify the activity of other proteins, such as NMDA receptors and the Na+,K+-ATPase pump, by nitrosylating them.

1.
Both electrical and chemical synapses play important roles in cellular communication within the mammalian nervous system.
2.
Electrical synapses establish direct connections between the cytosol of two neurons, enabling rapid bidirectional current flow. They function as low-pass filters.
3.
Gap junctions serve as the structural counterparts of electrical synapses and contain channels formed by hemichannels called connexons. Connexons are composed of connexins.
4.
Standard chemical synaptic transmission involves the release of a neurotransmitter from a presynaptic terminal, diffusion of the neurotransmitter across a synaptic cleft, and binding of the neurotransmitter to receptors on the adjacent postsynaptic membrane.
5.
The entry of calcium into the presynaptic terminal triggers the release of neurotransmitter. The release of neurotransmitter occurs in quantal fashion, as demonstrated by recording miniature endplate potentials (mEPPs) at the frog neuromuscular junction.
6.
Neurotransmitter is packaged into synaptic vesicles within the presynaptic terminal. These vesicles represent the quantal units. In other words, the release of neurotransmitter from a single vesicle produces one mEPP at the neuromuscular junction or, equivalently, one miniature postsynaptic potential (mPSP) at a central synapse.
7.
Multiple proteins are involved in the priming, docking, and fusion of synaptic vesicles. Synaptotagmin acts as the calcium sensor responsible for triggering vesicle fusion.
8.
Excitatory synapses increase the probability of postsynaptic neuron firing, while inhibitory synapses decrease this probability.
9.
The reversal potential is the membrane potential at which the net current flow through a ligand-gated channel reverses. Excitatory synapses generate depolarizing potentials known as excitatory postsynaptic potentials (EPSPs), which have reversal potentials positive to the spike threshold, often due to the opening of nonselective cation channels.
10.
Inhibitory synapses produce inhibitory postsynaptic potentials (IPSPs) that have reversal potentials more negative than the spike threshold but not necessarily negative to the resting potential. Inhibitory synapses can decrease the probability of neuronal firing through two mechanisms: membrane hyperpolarization and a decrease in the input resistance of the neuron, resulting in the shunting of synaptic currents.
Alabi AA, Tsien RW. Perspectives on kiss-and-run: role in exocytosis, endocytosis, and neurotransmission. Annu Rev Physiol. 2013;75:393-422.
11.
The process by which a neuron decides to generate an action potential in response to its inputs is referred to as synaptic integration. The summation of EPSPs and IPSPs can be highly nonlinear and depends on various factors, including the dendritic tree's geometry, the location of synaptic inputs relative to the initial segment, and the passive (RC) and active membrane properties of the cell.
12.
As is the case with the biogenic amines, receptors for the various peptides are essentially all of the metabotropic type and are coupled to G proteins that mediate effects via second messenger cascades. It is worth mentioning again that studies consistently show a mismatch between the locations of terminals containing a particular peptide and the receptors for it. Thus, these receptors are often activated by neurotransmitter diffusing through the extracellular space rather than at synapses. This implies that these receptors will experience much lower concentrations of agonist, and indeed, they are very sensitive to their agonists.
Unlike the other neurotransmitters that were covered, NO and CO do not bind to receptors. One way they do affect cell activity is to activate enzymes involved in second messenger cascades, such as guanylyl cyclase. In addition, NO has been shown to modify the activity of other proteins, such as NMDA receptors and the Na+,K+-ATPase pump, by nitrosylating them.
1.
Both electrical and chemical synapses are important means of cellular communication in the mammalian nervous system.
2.
Electrical synapses directly connect the cytosol of two neurons and allow rapid bidirectional current flow between neurons. They act as low-pass filters.
3.
Gap junctions are the morphological correlate of electrical synapses. Gap junctions contain channels formed by hemichannels called connexons. Connexons are formed by proteins called connexins.
4.
Standard chemical synaptic transmission involves the release of transmitter from a presynaptic terminal, diffusion of transmitter across a synaptic cleft, and binding of the transmitter to receptors on the apposed postsynaptic membrane.
5.
Entry of calcium into the presynaptic terminal triggers the release of neurotransmitter. Release of neurotransmitter is quantal, as first demonstrated by the recording of mEPPs at the frog neuromuscular junction.
6.
Transmitter is packaged into synaptic vesicles in the presynaptic terminal. The vesicles are the quantal elements. That is, the release of transmitter from one vesicle causes a mEPP at the neuromuscular junction or, equivalently, one mPSP at a central synapse.
7.
Many proteins are involved in priming, docking, and fusion of synaptic vesicles. Synaptotagmin is the Ca++ sensor for triggering vesicle fusion.
8.
Excitatory and inhibitory synapses increase or decrease, respectively, the probability that the postsynaptic neuron will spike.
9.
The reversal potential is the membrane potential at which net current flow through a ligand-gated channel reverses. Excitatory synapses generate depolarizing potentials (EPSPs) that have reversal potentials positive to the spike threshold, most often as a result of the opening of nonselective cation channels.
10.
Inhibitory synapses generate IPSPs that have reversal potentials more negative than the spike threshold but not necessarily negative to the resting potential. Inhibitory synapses can decrease spike probability by two mechanisms: hyperpolarization of the membrane and a decrease in the input resistance of the neuron, leading to a shunt of synaptic currents.
Alabi AA, Tsien RW. Perspectives on kiss-and-run: role in exocytosis, endocytosis, and neurotransmission. Annu Rev Physiol. 2013;75:393-422.
11.
The process by which a neuron decides to fire an action potential as a result of its inputs is referred to as synaptic integration. The summation of EPSPs and IPSPs can be highly nonlinear and depends on many factors, including the geometry of the dendritic tree, location of the synaptic inputs relative to the initial segment, and the passive (RC) and active membrane properties of the cell.
12.