Neurotransmitter transporters: new insights into structure, function and pharmacology

Neurotransmitter transporters on neurons and glial cells catalyze the uptake of neurotransmitter, and may serve to limit the activation of receptors during synaptic signaling. Over the past few years significant progress has been made toward a molecular understanding of neurotransmitter transporters in the CNS. The plasma membrane neurotransmitter carriers are comprised of two structurally- and mechanistically-distinct gene families, the Na+ and Cl(-)-dependent transporters that include the carriers for most of the classical CNS neurotransmitters and several additional carriers for amino acids and other substrates outside the nervous system. A second structurally distinct family of Na(+)-dependent carriers encompasses the excitatory amino acid transporters. For both carrier families the transport of substrate is coupled to the cotransport of sodium ions down a concentration gradient. Electrophysiological studies of neurotransmitter transporters indicate that many of the carriers are electrogenic and may operate in some ways similar to ion channels. In addition, emerging data indicate that these carriers not only function in the uptake of neurotransmitter, but also that as a consequence of their ability to alter the membrane potential they may have a broader role in regulating neuronal excitability and signaling mechanisms.