Neurotransmitter-gated ion channels at fast chemical synapses: from structure to pathology

CECILIA BEATRIZ BOUZAT

Physiological Minireviews

Argentine Physiological Society

Año: 2005 vol. 1 p. 35 - 47

1669-5402

The human brain is a vast and complicated network, where billions of nerve cells use signals to communicate with each other. Signals must be rapid and precise. Within a neuron, this speed is achieved using electrical signals that are conducted along extended, cable-like processes. At chemical synapses, these electrical signals are first converted into chemical signals by the release of neurotransmitter into a narrow synaptic gap after depolarization of the presynaptic cell. Neurotransmitter-gated ion channels at the postsynaptic cell, which act as complete signal-transduction systems, reconvert signals from chemical to electrical in under one millisecond. After the transmitter is released and binds to an extracellular region of the receptor, the channel opens to excite or inhibit the train of postsynaptic action potentials. Just as important, the channel closes within a few milliseconds as the transmitter dissociates to terminate the synaptic event. Chemical synaptic transmission offers the advantages of signal amplification, reversal of signal polarity and greater potential for modulation, all important properties for higher brain function. Pentameric neurotransmitter-gated ion channels (LGICs) play key roles in chemical synapses throughout the nervous system, and include receptors activated by acetylcholine (ACh), g-aminobutyric acid, glycine and serotonin (5-HT) (LeNovere and Changeux, 2001; Lester et al., 2004). They are known as the Cys-loop receptors because all family subunits contain in their amino-terminal, extracellular halves, a pair of disulfide-bonded cysteines, which are separated by 13 residues. Their vital role in converting chemical recognition into an electrical impulse makes these receptors prime loci for learning, memory and disease processes, as well as targets for clinically relevant drugs. Over the past 30 years, LGICs have been the major targets of the most commonly prescribed drugs, such as neuromuscular blockers, barbiturates and benzodiazepines. In the last years an ever increasing number of human and animal diseases have been found to be caused by defective ion channel function of Cys-loop receptors.