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Part of the book series: Neuromethods ((NM,volume 112))

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Abstract

Current kinetics takes into account three key components of receptor function. They include an open or activated state, a deactivated state, and a desensitized state (Fig. 1) As the ligand binds to the receptor, a conformational change takes place allowing pore formation and ion permeability, defining an activated state. The deactivated state refers to a receptor transitioning from a bound to an unbound agonist state with decreasing ionic permeability as the channel closes. This process occurs as the agonist concentration becomes zero. Finally, a desensitized state refers to a reduced response to an agonist often due to prolonged agonist exposure (i.e., the receptor is in a non-conducting state despite agonist being bound to the receptor). Desensitization can be altered by neurotransmitter clearance from the synaptic cleft via diffusion, degradation, or reuptake through transporters expressed on neuronal or glial cells. Prolonged exposure to neurotransmission may induce desensitization of receptors, while rapid removal of the neurotransmitter from the synaptic cleft may reduce desensitization.

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Notes

  1. 1.

    There are two other key components to receptor function, which include inactivation and sensitization. When a channel/receptor loses permeability to an ion or is unable to activate downstream signaling processes in the presence of an agonist, it is considered inactive. An example is the “ball and chain” model of inactivation in which inactivation is caused by peptide (the ball) insertion into the open channel pore, thus blocking ion flow through the channel [1]. Sensitization, on the other hand, refers to a potentiated response to a given stimulus. For example, administration of an agonist at the same concentration previously used can trigger greater postsynaptic currents in sensitized receptors.

  2. 2.

    In addition to GABAARs there are GABACRs, which are mainly located in the retina and are composed of rho subunits. Since 2008, it is recommended that GABACRs become known as GABAA-ρ [88].

  3. 3.

    During embryonic development and at birth GABAARs and GlyRs play different roles in regulating membrane potentials. Their activation elicits depolarization of membrane voltage causing the cell to become more excitable. This effect is due to the positive chloride equilibrium potential, which results in the efflux of chloride from the postsynaptic cell upon receptor activation.

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Graziane, N., Dong, Y. (2016). Kinetics of Synaptic Current. In: Electrophysiological Analysis of Synaptic Transmission. Neuromethods, vol 112. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3274-0_17

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