Regulation of Neurotransmitter Release by Presynaptic Receptors

The release of neurotransmitter is subject to powerful modulatory control by receptors located in or near the presynaptic terminal. These presynaptic receptors are a diverse group of proteins, but they can be broadly divided into two classes: metabotropic receptors and ionotropic receptors. Most metabotropic receptors are coupled to G proteins and inhibit release by an interaction between G protein βγ-subunits and calcium channels; in contrast, ionotropic receptors affect release mainly by changing the presynaptic membrane potential. Accumulating evidence suggests that ionotropic receptors may also engage metabotropic cascades under some conditions. Presynaptic receptors can functionally reshape neural circuits by rapidly and reversibly changing the properties of synaptic transmission, and the specific expression of different receptors at different synapses allows each receptor subtype to have a distinct effect on neural processing.