In the somatic and dendritic compartments of many adult neurons at rest, i is maintained at only a few millimoles. Therefore, regarding the role of ion transport in controlling the efficacy of inhibition, the determining factor is the capability of Cl −-extruding mechanisms to maintain the reversal potentials of GABA AR- and GlyR-mediated responses, E GABA and E Gly, at a sufficiently negative level to prevent the neuron from firing action potentials. The strength of the inhibitory action of GABA ARs and GlyRs is determined not only by the respective conductances, but also by the efficacy of Cl − extrusion. Upon receptor binding and channel opening, the electrochemical driving force determines whether the current carried by Cl − is hyperpolarizing or depolarizing. Role of neuronal Cl − homeostasis in GABA/glycinergic signalingįast synaptic inhibition in the adult CNS is largely mediated via ionotropic GABA ARs and GlyRs, ligand-gated anion channels permeable to Cl −, cf. The molecular mechanisms that regulate i and the dynamic changes in GABA AR and GlyR signaling during CNS development, synaptic activity, and in neurological diseases are only beginning to be understood. Although there have been many investigations of GABA AR modulation as a determinant of inhibitory synaptic strength, less attention has been paid to the functional effects of Cl − transporter regulation. The homeostasis of intraneuronal Cl − concentration i, established by the dynamic functional regulation of Cl − channels, transporters, and exchangers, is a prime determinant of GABA and glycine function, and endows GABA ARs and GlyRs with a unique functional plasticity ( Box 1). Modulation of KCC2 activity underlies dynamic changes in neuronal Cl − homeostasis and GABAergic signaling during development and in diseaseįast synaptic inhibition in the adult central nervous system (CNS) is chiefly mediated via GABA ARs and GlyRs, which are ligand-gated Cl − channels cf.

Cl studio liliya