The release of neurotransmitter molecules occurs after vesicle fusion. These molecules diffuse rapidly across the synaptic cleft and bind to receptors on the postsynaptic membrane. This binding leads to the opening or closing of ion channels, which are known as ligand-gated channels. Unlike voltage-gated channels that are influenced by membrane potential, ligand-gated channels are primarily controlled by neurotransmitter binding. However, there are certain channels, such as the NMDA channel, that are both ligand and voltage gated.

It is important to note that the following information pertains to ionotropic receptors where the ion channel is a part of the receptor itself. This type of receptor is responsible for "fast" synaptic transmission. In contrast, "slow" synaptic transmission occurs through metabotropic receptors, where the receptor and ion channel are separate molecules. When neurotransmitter binds to the receptor, biochemical cascades are initiated, leading to postsynaptic potentials with slower onsets. Despite the differences in time courses, many fundamental principles apply to both types of postsynaptic potential.

EPSPs, or excitatory postsynaptic potentials, occur when neurotransmitter binding changes the membrane potential of the postsynaptic cell and increases its excitability. On the other hand, IPSPs, or inhibitory postsynaptic potentials, inhibit the firing of action potentials in the neuron. EPSPs are always depolarizing potentials, while IPSPs are usually hyperpolarizing.

Once a ligand-gated channel is open, the direction of current flow is determined by the electrochemical driving force for the permeant ion(s). Most channels underlying EPSPs have relatively large pores, allowing the passage of cations with similar ease. For example, consider the acetylcholine-gated channel at the neuromuscular junction. Since Na+ and K+ are the major cations present, the net current through the channel is the sum of the Na+ and K+ currents. The current through a channel depends on the conductance of the channel to the ion and the driving force on the ion. The equation gx = (Vm - Ex) expresses this relationship, where gx represents the channel conductance to ion x, Vm is the membrane potential, and Ex is the Nernst equilibrium potential for ion x. In the case of the acetylcholine-gated channel, gx is similar for Na+ and K+, so the main determinant of net current is the relative driving forces (Vm - Ex). When the membrane is at its resting potential (typically around -70 mV), there is a strong driving force for Na+ to enter the cell, while there is only a small driving force for K+ to leave the cell. Therefore, if acetylcholine-gated channels open at the resting potential, a large inward Na+ current and a small outward K+ current flow through the acetylcholine channel, resulting in a net inward current that depolarizes the membrane.

The net inward current resulting from the opening of such channels is referred to as the excitatory postsynaptic current (EPSC).
Following vesicle fusion the neurotransmitter molecules are released and diffuse across the synaptic cleft (a very rapid process) and bind to receptors on the postsynaptic membrane. This binding leads to the opening (or less often the closing) of ion channels. These channels are termed ligand-gated because their opening and closing are primarily controlled by the binding of neurotransmitter. This mechanism can be contrasted with that of the voltage-gated channels underlying the action potential, whose opening and closing are determined by the membrane potential. However, there are some channels, most notably the NMDA (N-methyl-Daspartate) channel, that are both ligand and voltage gated.
It is also worth noting here that what follows in this section refers to what happens when neurotransmitter binds to receptors in which the ion channel is part of the receptor itself. These receptors are referred to as ionotropic receptors and underlie what is now called “fast” synaptic transmission. There is also “slow” synaptic transmission, mediated by what are called metabotropic receptors, in which the receptor and ion channel are not part of the same molecule, and binding of neurotransmitter to the receptor initiates biochemical cascades that lead to postsynaptic potentials with slow onsets (see the section Receptors for details). Despite the differing time courses, many of the same basic principles apply to both types of postsynaptic potential.
EPSPs. As stated earlier, the binding of neurotransmitter generally changes the membrane potential of the postsynaptic cell, and these changes are referred to as EPSPs when they increase the excitability of the neuron and IPSPs when they inhibit the neuron from firing action potentials. EPSPs are always depolarizing potentials, and IPSPs are usually hyperpolarizing.
Once a ligand-gated channel is open, the direction of current flow through it is determined by the electrochemical driving force for the permeant ion(s). It turns out that the pores of most channels that underlie EPSPs are relatively large and therefore allow passage of most cations with similar ease. As an example, consider the acetylcholinegated channel that is opened at the neuromuscular junction. Na+ and K+ are the major cations present (Na+ extracellularly and K+ intracellularly); therefore, the net current through the channel is approximately the sum of the Na+ and K+ currents (Inet = INa + IK). Recall that the current through a channel from a particular ion is dependent on two factors: the conductance of the channel to the ion and the driving force on the ion. This relationship is expressed by the equation
Equation 6.1 where gx is the conductance of the channel to ion x, Vm is the membrane potential, and Ex is the Nernst equilibrium potential for ion x. In this case gx is similar for Na+ and K+ , so the main determinant of net current is the relative driving forces (Vm − Ex). If the membrane is at its resting potential (typically around −70 mV), there is a strong driving force (Vm − ENa) for Na+ to enter the cell because this potential is far from the Na+ Nernst potential (about +55 mV), whereas there is only a small driving force for K+ to leave the cell because Vm is close to the K+ Nernst potential (about −90 mV). Thus, if acetylcholine-gated channels open when the membrane is at its resting potential, a large inward Na+ current and a small outward K+ current will flow through the acetylcholine channel, thereby resulting in a net inward current, which acts to depolarize the membrane.
The net inward current that results from opening such channels is called the excitatory postsynaptic current (EPSC).