The time course of fast synaptic transmission is illustrated in Fig. 6.7A, which compares the duration of the excitatory postsynaptic current (EPSC) and the resulting excitatory postsynaptic potential (EPSP). The EPSC is relatively short-lived, lasting approximately 1 to 2 milliseconds, representing the duration that the channels are open. This brevity is attributed to the neurotransmitter being quickly degraded by enzymes or taken up by glia or neurons in the synaptic cleft. The binding and unbinding of neurotransmitters to receptors occur rapidly, so when their concentration decreases in the cleft, the postsynaptic receptor channels swiftly close, thus terminating the EPSC. Notably, the end of the EPSC corresponds to the peak of the EPSP, followed by a prolonged tail. The duration of this tail and the rate at which the EPSP amplitude decays are influenced by the passive membrane properties of the cell, specifically its RC properties.

In slow synaptic transmission, the duration of the EPSP primarily reflects the activation and deactivation of biochemical processes rather than the membrane properties. Even in fast EPSPs, which are relatively longer in duration compared to EPSCs and action potentials, this extended timeframe holds functional significance as it allows for the overlapping and summation of EPSPs. Such summation plays a central role in the integrative properties of neurons.

Consider a scenario where the channels responsible for generating action potentials are blocked, and the membrane of the postsynaptic cell is experimentally depolarized through the injection of current via an intracellular electrode. This experimental depolarization reduces the driving force for Na+ while increasing it for K+. When the synapse is activated at this point, the net current passing through the receptor channel (the EPSC) will be smaller due to changes in the relative driving force. Consequently, if the membrane potential is sufficiently depolarized, there will come a point where the Na+ and K+ currents through the channel balance each other, resulting in no net current and no EPSP. If the membrane is further depolarized beyond this point, a net outward current flows through the receptor channels, causing membrane hyperpolarization (i.e., the EPSP becomes negative). This potential, at which there is no EPSP (or EPSC), is referred to as the reversal potential. For excitatory synapses, the reversal potential is typically around 0 mV (±10 mV), depending on the specific synapse.

It is worth emphasizing that the presence of a reversal potential serves as a crucial criterion for establishing the chemical-gated nature of a synaptic response, as opposed to voltage-gated channels. Currents through voltage-gated channels do not reverse, except at the Nernst potential of the selective ion (and only when the channel is open at that potential). Consequently, beyond a certain membrane potential, voltage-gated channels remain closed, resulting in no current flow. In contrast, ligand-gated channels can open at any membrane potential, allowing for a continuous net current flow through them, except at a specific voltage point, known as the reversal potential.
Fig. 6.7A contrasts the time course of the EPSC and the resulting EPSP for fast synaptic transmission. The EPSC is much shorter (≈1 to 2 msec in duration) and corresponds to the time the channels are actually open. The short duration of the EPSC is due to the fact that the released neurotransmitter remains in the synaptic cleft for only a short while before being either enzymatically degraded or taken up by either glia or neurons. Binding and unbinding of a neurotransmitter to its receptor take place rapidly, so once its concentration falls in the cleft, the postsynaptic receptor channels rapidly close as well and terminate the EPSC. Note how the end of the EPSC corresponds to the peak of the EPSP, which is followed by a long tail. The duration of the tail and the rate of the decay in EPSP amplitude reflect the passive membrane properties of the cell (i.e., its RC properties) (see ). In slow synaptic transmission, the duration of the EPSP reflects the activation and deactivation of biochemical processes more than the membrane properties. The long duration of even fast EPSPs (relative to EPSCs and action potentials) is functionally important because it allows EPSPs to overlap and thereby summate. Such summation is central to the integrative properties of neurons (see the next section,
Normally an EPSP depolarizes the membrane, and if this depolarization reaches threshold, an action potential is generated. However, consider what happens if the channels underlying the action potential are blocked and the membrane of the postsynaptic cell is experimentally depolarized by injecting current through an intracellular electrode. Because the membrane potential is now more positive, the driving force for Na+ is decreased and that for K+ increased. If the synapse is activated at this point, the net current through the receptor channel (the EPSC) will be smaller because of changes in the relative driving force. This implies that if the membrane potential is depolarized enough, there will be a point at which the Na+ and K+ currents through the channel are equal and opposite, and thus there is no net current and no EPSP. If the membrane is depolarized beyond this point, there is a net outward current through the receptor channels and the membrane will hyperpolarize (i.e., the EPSP will be negative). Thus, the potential at which there is no EPSP (or EPSC) is known as the reversal potential. For excitatory synapses, the reversal potential is usually around 0 mV (±10 mV), depending on the synapse (see
Fig. 6.7B–C
It is worth noting that a reversal potential is a key criterion for demonstrating the chemical-gated as opposed to the voltage-gated nature of a synaptic response because currents through voltage-gated channels do not reverse, except at the Nernst potential of the ion for which they are selective (and then only if the channel is open at that potential). Consequently, beyond a certain membrane potential, no current will flow through voltage-gated channels because they will be closed. In contrast, ligand-gated channels can be opened at any membrane potential and thus can always have a net current flow through them, except at one specific voltage, the reversal potential.