Monoaminergic and GABAergic transporters (MATs and GATs)

Monoaminergic and GABAergic transporters are a group of integral membrane proteins, primarily belonging to the Solute Carrier Family 6 (SLC6), that regulate the concentrations of key neurotransmitters in the central nervous system (Kristensen et al., 2011). The monoaminergic subgroup includes the serotonin (SERT), norepinephrine (NET), and dopamine (DAT) transporters, while the GABAergic subgroup consists of various GABA transporters such as GAT-1, GAT-2, and GAT-3 (Pramod et al., 2013; Zhou & Danbolt, 2013). Their primary biological function is the reuptake of neurotransmitters from the synaptic cleft back into the presynaptic neuron or surrounding glial cells, effectively terminating the synaptic signal and recycling the transmitter for future use (Bermingham & Blakely, 2016). Dysfunction in these transport systems is heavily implicated in the pathophysiology of numerous psychiatric and neurological conditions, including depression, anxiety, ADHD, and epilepsy (Iversen, 2006). Consequently, they are among the most successful therapeutic targets in pharmacology, with drugs like selective serotonin reuptake inhibitors (SSRIs) and stimulants modulating their activity to restore neurochemical balance (Bröer & Gether, 2012). However, targeting these systems requires careful management due to risks such as serotonin syndrome, cardiovascular stimulation, and potential for substance misuse (Volkow et al., 2003).

Other names

SLC6 neurotransmitter transportersSodium- and chloride-dependent neurotransmitter transportersMonoamine transporters (MATs)GABA transporters (GATs)

These transporters function by coupling the movement of neurotransmitters (serotonin, norepinephrine, dopamine, or GABA) against their concentration gradient to the movement of sodium and chloride ions down their electrochemical gradients (Kristensen et al., 2011). Drugs typically act as competitive or non-competitive inhibitors, blocking the reuptake of these neurotransmitters and thereby increasing their concentration and residence time in the synaptic cleft to enhance downstream signaling (Bermingham & Blakely, 2016).