Ion Channels & Neurotransmitter receptors ~ Drugs & Therapeutics

On the basis of mechanism of controlling opening and closing of a channel nerve cell membranes contain two types of channels:

Voltage gated channels
Ligand gated channels

Voltage gated channel:

They respond to the change in the membrane potential of the cell. In nerve cells these channels are concentrated on the initial segment and the axon and are responsible for the fast action potential, which transmit the signal from cell body to nerve terminal. There are many types of voltage sensitive calcium and potassium channels on the cell body, dendrites, and initial segment which act on a much slower time scale and modulate the rate at which the neuron discharges. For e.g some types of potassium channels opened by depolarization of the cell results in slowing of further depolarization and act as a brake to limit further action potential discharge.

Ligand gated channel:
Neurotransmitters exert their effects on neurons by binding to two distinct classes of receptor. These two classes are; ligand-gated channels, or ionotropic receptors and the second one is metabotropic receptors.

Ionotropic receptors consists of subunits, and binding of ligand directly opens the channel, which is an integral parts of the receptor complex. These channels are insensitive or only weakly sensitive to membrane potential. Activation of these channels typically results in a brief (a few milliseconds to tens of milliseconds) opening of the channel. Ligand-gated channels are responsible for fast synaptic transmission typical of hierarchical pathways in the CNS.

Metabotropic receptors are 7-transmembrane G protein-coupled receptors. The binding of neurotransmitter to this type of receptor does not result in the direct gating of a channel. Rather, binding to the receptor engages a G protein, which results in the production of second messengers that modulate voltage-gated channels. These interactions can occur entirely with the plane of the membrane and are referred to as membrane-delimited pathways. In this case, the G protein (often the subunit) interacts directly with the voltage-gated ion channel. In general, two types of voltage-gated ion channels are the targets of this type of signaling: calcium channels and potassium channels. When G proteins interact with calcium channels, they inhibit channel function. This mechanism accounts for the presynaptic inhibition that occurs when presynaptic metabotropic receptors are activated. In contrast, when these receptors are postsynaptic, they activate potassium channels, resulting in a slow postsynaptic inhibition. Metabotropic receptors can also modulate voltage-gated channels less directly by the generation of diffusible second messengers. A classic example of this type of action is provided by the adrenoceptor, which generates cAMP via the activation of adenylyl cyclase. Whereas membrane-delimited actions occur within microdomains in the membrane, second messenger-mediated effects can occur over considerable distances. Finally, an important consequence of the involvement of G proteins in receptor signaling is that, in contrast to the brief effect of ionotropic receptors, the effects of metabotropic receptor activation can last tens of seconds to minutes. Metabotropic receptor predominate in the diffuse neuronal systems in the CNS.