Pathway: GABA receptor activation
Reactions in pathway: GABA receptor activation :
GABA receptor activation
Gamma aminobutyric acid (GABA) receptors are the major inhibitory receptors in human synapses. They are of two types. GABA A receptors are fast-acting ligand gated chloride ion channels that mediate membrane depolarization and thus inhibit neurotransmitter release (G Michels et al Crit Rev Biochem Mol Biol 42, 2007, 3-14). GABA B receptors are slow acting metabotropic Gprotein coupled receptors that act via the inhibitory action of their Galpha/Go subunits on adenylate cyclase to attenuate the actions of PKA. In addition, their Gbeta/gamma subunits interact directly with N and P/Q Ca2+ channels to decrease the release of Ca2+. GABA B receptors also interact with Kir3 K+ channels and increase the influx of K+, leading to cell membrane hyperpolarization and inhibition of channels such as NMDA receptors (A Pinard et al Adv Pharmacol, 58, 2010, 231-55).
Chemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a presynaptic neuron and a postsynaptic neuron, muscle cell or glad cell. The pre and the postsynaptic cell are separated by a gap (space) of 20 to 40 nm called the synaptic cleft. The signals pass in a single direction from the presynaptic to postsynaptic neuron (cell). The presynaptic neuron communicates via the release of neurotransmitter which bind the receptors on the postsynaptic cell. The process is initiated when an action potential invades the terminal membrane of the presynaptic neuron.
Action potentials occur in electrically excitable cells such as neurons and muscles and endocrine cells. They are initiated by the transient opening of voltage dependent sodium channels, causing a rapid, large depolarization of membrane potentials that spread along the axon membrane.
When action potentials arrive at the synaptic terminals, depolarization in membrane potential leads to the opening of voltage gated calcium channels located on the presynaptic membrane. The external Ca2+ concentration is approximately 10-3 M while the internal Ca2+ concentration is approximately 10-7 M. Opening of calcium channels causes a rapid influx of Ca2+ into the presynaptic terminal. The elevated presynaptic Ca2+ concentration allows synaptic vesicles to fuse with the plasma membrane of the presynaptic neuron and release their contents, neurotransmitters, into the synaptic cleft. These diffuse across the synaptic cleft and bind to specific receptors on the membrane of the postsynaptic cells. Activation of postsynaptic receptors upon neurotransmitter binding can lead to a multitude of effects in the postsynaptic cell, such as changing the membrane potential and excitability, and triggering intracellular signaling cascades.
Action potentials occur in electrically excitable cells such as neurons and muscles and endocrine cells. They are initiated by the transient opening of voltage dependent sodium channels, causing a rapid, large depolarization of membrane potentials that spread along the axon membrane.
When action potentials arrive at the synaptic terminals, depolarization in membrane potential leads to the opening of voltage gated calcium channels located on the presynaptic membrane. The external Ca2+ concentration is approximately 10-3 M while the internal Ca2+ concentration is approximately 10-7 M. Opening of calcium channels causes a rapid influx of Ca2+ into the presynaptic terminal. The elevated presynaptic Ca2+ concentration allows synaptic vesicles to fuse with the plasma membrane of the presynaptic neuron and release their contents, neurotransmitters, into the synaptic cleft. These diffuse across the synaptic cleft and bind to specific receptors on the membrane of the postsynaptic cells. Activation of postsynaptic receptors upon neurotransmitter binding can lead to a multitude of effects in the postsynaptic cell, such as changing the membrane potential and excitability, and triggering intracellular signaling cascades.
The human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication among this astronomical number of elements. This communication occurs across synapses, the functional connection between neurons. Synapses can be divided into two general classes: electrical synapses and chemical synapses. Electrical synapses permit direct, passive flow of electrical current from one neuron to another. The current flows through gap junctions, specialized membrane channels that connect the two cells. Chemical synapses enable cell-to-cell communication using neurotransmitter release. Neurotransmitters are chemical agents released by presynaptic neurons that trigger a secondary current flow in postsynaptic neurons by activating specific receptor molecules. Neurotransmitter secretion is triggered by the influx of Ca2+ through voltage-gated channels, which gives rise to a transient increase in Ca2+ concentration within the presynaptic terminal. The rise in Ca2+ concentration causes synaptic vesicles (the presynaptic organelles that store neurotransmitters) to fuse with the presynaptic plasma membrane and release their contents into the space between the pre- and postsynaptic cells.