Specialized neurotransmitter transporters in astrocytes

In the central nervous system (CNS), synaptic neurotransmission is a fundamental and critical process for neurons to receive and process information. In this process, neurotransmitters, the chemical signals, are released from presynaptic neuronal terminals upon stimulus to activate receptors on postsynaptic membranes. The inactivation of most released neurotransmitters occurs via efficient reuptake of neurotransmitters into the presynaptic nerve terminal and/or adjacent glial cells. Astrocytes, the most abundant cell in the CNS, express various transporter proteins on the plasma membrane for the uptake of neurotransmitters, forming an indispensable unit of functional synaptic neurotransmission. Transporters are vital for the normal CNS physiology by maintaining neurotransmitter homeostasis, modulating synaptic transmission and preventing neurological damage induced by the imbalance of neurotransmitters. The distribution and functional importance of neurotransmitter transporters in neurons or astrocytes varies by individual neurotransmitters. For glutamate, transporters are present in both neurons and astrocytes but astroglial glutamate transporters are functionally dominant (Rothstein et al., 1994; Danbolt, 2001); for γ-aminobutyric acid (GABA) and glycine, both neuronal and astrocytic transporters are functionally dominant and their functions are complementary (Chen et al., 2004a; Betz et al., 2006); for monoamine (dopamine, serotonin, and norepinephrine) transmitters, transporters are mainly expressed in the cognate neurons not in astrocytes (Torres et al., 2003). In this chapter, the principal focus will be on astrocytes, the various neurotransmitter transporters they express, and the role of astroglial transporter dysfunction in disease.