Calcium permeability of ligand-gated Ca2+ channels

Many of cation-permeable ionotropic receptors to various neurotransmitters, such as glutamate, acetylcholine and ATP, are permeable to Ca2+ ions. For some of them, in particular NMDA, nicotinic Ach and P2X receptors, permeability to Ca2+ is higher than permeability to monovalent cations. Such receptors can be viewed as ligand-gated Ca2+-channels (LGCCs). This review provides an overview of past works on structure LGCCs, including structural motifs responsible for their interaction with Ca2+ ions, and functional implications of their Ca2+-permeability. The NMDA, P2X and nicotinic Ach receptors are abundantly expressed in the central nervous system. They are present at the nerve terminals, postsynaptic, extrasynaptic and glial membrane and therefore can contribute to synaptic function at different levels. Their heteromeric structure leads to wide variety of LGCC subtypes and great diversity of their functional properties. The influx of Ca2+ provided by LGCCs can activate a plethora of secondary messenger cascades, which can modulate activity, trafficking and lateral mobility of LGCCs and thereby are entangled with their physiological function. In the discussion of the physiological importance of LGCCs we are focusing on emerging evidence on their role in control of synaptic transmission, plasticity and glia–neuron interaction.