Metabotropic receptors

Based on their structural and functional characteristics, neurotransmitter receptors can be classified into two broad categories: metabotropic and ionotropic receptors. In contrast to the latter, metabotropic receptors do not form an ion channel pore; rather, they are indirectly linked with ion-channels on the plasma membrane of the cell through signal transduction mechanisms. This class of receptors includes the metabotropic glutamate receptors, muscarinic acetylcholine receptors, GABAB receptors, and most serotonin receptors, as well as receptors for norepinephrine, epinephrine, histamine, neuropeptides (Austin, 2004; Purves et al., 2001) and dopamine (Zimmerberg, 2002).

All metabotropic receptors are monomeric proteins with seven transmembrane domains. The protein's N terminus is on the extracellular side of the membrane and its C terminus is on the intracellular side (Purves et al., 2001).

Metabotropic receptors have neurotransmitters as ligands, which, when bound to the receptors, initiate cascades that can lead to channel-opening or other cellular effects. When a ligand, also called the primary messenger, binds to the receptor, or the transducer, the latter activates a primary effector, which can go on to activate secondary messengers or have other effects. Since opening channels by metabotropic receptors involves activating a number of molecules in turn, channels associated with these receptors take longer to open than ionotropic receptors do, and they are thus not involved in mechanisms that require quick responses (Kandel et al., 2000, p. 240). However, metabotropic receptors also remain open from seconds to minutes (Kandel et al., 2000, p. 250-251). Thus they have a much longer-lasting effect than ionotropic receptors, which open quickly but only remain open for a few milliseconds (Austin, 2004). While ionotropic channels have an effect only in the immediate region of the receptor, the effects of metabotropic receptors can be more widespread through the cell.

Metabotropic receptors can both open and close channels. They can make a membrane more excitable by closing K+ channels, retaining positive charge within the cell and thus reducing the amount of current necessary to cause an action potential (Kandel et al., 2000, p. 242-243). Metabotropic receptors on the presynaptic membrane can inhibit or, more rarely, facilitate neurotransmitter release from the presynaptic neuron (Schmitz et al., 2001). These receptors can be further classified into tyrosine kinases and G-protein-coupled receptors, or GPCRs (Kandel et al., 2000, p. 229).