The Role of Chloride Transport in Postsynaptic Inhibition of Hippocampal Neurons

Abstract

Hippocampal inhibitory postsynaptic potentials are depolarizing in granule cells but hyperpolarizing in CA3 neurons because the reversal potentials and membrane potentials of these cells differ. Here the hippocampal slice preparation was used to investigate the role of chloride transport in these inhibitory responses. In both cell types, increasing the intracellular chloride concentration by injection shifted the reversal potential of these responses in a positive direction, and blocking the outward transport of chloride with furosemide slowed their recovery from the injection. In addition, hyperpolarizing and depolarizing inhibitory responses and the hyperpolarizing and depolarizing responses to the inhibitory neurotransmitter gamma-aminobutyric acid decreased in the presence of furosemide. These effects of furosemide suggest that the internal chloride activity of an individual hippocampal neuron is regulated by two transport processes, one that accumulates chloride and one that extrudes chloride.

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

“…Several mechanisms may contribute to these GABA A receptor-mediated potentials. First, accumulation of intracellular Cl − ([Cl − ] i ) -eventually favored by decreased KCC2 activity -can shift the E GABA to values positive to resting membrane potential; indeed, since dendritic receptor activation often produces depolarization, it was proposed that [Cl − ] i in cortical cell dendrites could be higher than in the soma, where hyperpolarizations are commonly recorded (Misgeld et al, 1986). Second, [Cl − ] i accumulation is caused (at least in immature neurons) by the activation of NKCC1 cotransporter that imports Na + , K + , and Cl − (Achilles et al, 2007;Sipilä et al, 2009).…”

Theta-bursts induce a shift in reversal potentials for GABA-A receptor-mediated postsynaptic currents in rat hippocampal CA1 neurons

“…In neonatal neurons, RPs for GABA-ergic PSCs are such that the amino acid is excitatory on central neurons (Chen et al, 1996;Luhmann and Prince, 1991;Misgeld et al, 1986). This excitatory action has been suggested to substitute for AMPA-receptor mediated depolarization of postsynaptic neurons in facilitating glutamatergic synaptic plasticity through the removal of the Mg 2+ block of the NMDA receptor (Cherubini et al, 1991).…”

“…The RP of GABA-ergic PSCs is also generally thought to stabilize in adult neurons making the PSC hyperpolarizing at resting membrane potentials. As can be seen in the current study, the RP for the PSC in adult neurons does shift following a theta-burst stimulation indicating that there is still plasticity in the RP of adult neuronal GABA-ergic PSCs.In neonatal neurons, RPs for GABA-ergic PSCs are such that the amino acid is excitatory on central neurons (Chen et al, 1996;Luhmann and Prince, 1991;Misgeld et al, 1986). This excitatory action has been suggested to substitute for AMPA-receptor mediated depolarization of postsynaptic neurons in facilitating glutamatergic synaptic plasticity through the removal of the Mg 2+ block of the NMDA receptor (Cherubini et al, 1991).…”

A Furosemide-Sensitive K+–Cl−Cotransporter Counteracts Intracellular Cl−Accumulation and Depletion in Cultured Rat Midbrain Neurons

“…Indeed, GABA A receptor-mediated hyperpolarizing and /or depolarizing postsynaptic potentials have been observed (for review, see Kaila, 1994;Thompson, 1994). Some findings suggest variations in intracellular [C l Ϫ ] between different neurons and even a distinct C l Ϫ distribution in different compartments of a single neuron (Misgeld et al, 1986). Depolarizing GABA A responses, however, can be caused by bicarbonate efflux in combination with C l Ϫ influx or combined Cl Ϫ and HCO 3 Ϫ efflux (Grover et al, 1993;Kaila, 1994;Thompson, 1994;Staley et al, 1995;Perkins and Wong, 1996;Kaila et al, 1997).…”