Slow Synaptic Transmission

In addition to fast synaptic inputs there are slow synaptic inputs. These slow synaptic inputs are mediated by G protein-coupled receptors. For a long time, it was not understood how these slow synaptic inputs worked.

One key to understanding slow synaptic transmission was the recognition that these receptors modify the function of voltage-gated ion channels. This was first shown in neurons by Paul Adams, a Professor at Stony Brook. He discovered that one key target for the muscarinic receptor was a voltage-gated potassium channel called the M-channel (M for muscarine sensitive).

In the experiment shown in Figure 1 a neuron’s response to increasing amounts of injected current is shown. In the control case, with no drug, only a single action potential is elicited by the injected current. After addition of muscarine, which mimics the effect of acetylcholine on these neurons, the neuron is much more excitable.

Figure 1 Effect of muscarine on neuronal firing properties.

Muscarine activates muscarinic acetylcholine receptors that act through G-proteins to inhibit the M-channel. In general, inhibiting K⁺ channels will make a neuron more excitable and activating them will make the cell less excitable. In this way slow synaptic inputs can modulate the excitability of a given neuron over time.

There is an interplay between the slow and fast synaptic inputs. The fast excitatory synaptic inputs will have a larger effect on a neuron after it has received an excitatory neuromodulatory input than before, similar to that shown in Figure 1. The response of the neurons is dependent both on the nature of the fast synaptic inputs that it receives and how the excitability has been modulated by prior slow synaptic inputs.