Electrophysiology of GABAA and GABAB receptor subtypes

Bormann, Joachim

doi:10.1016/0166-2236(88)90156-7

Cited by 630 publications

(304 citation statements)

References 35 publications

Supporting

Mentioning

280

Contrasting

Unclassified

Order By: Relevance

“…e) GABA B receptors GABA B receptors are seven transmembrane receptors that are coupled to G-proteins and activate second messenger systems and Ca ++ and K + ion channels 225 . Three GABA B receptor proteins have been cloned and these resemble metabotropic GluRs 199,226 . GABA B receptors are heterooligomeric receptors made up of a mixture of a combination of the subunits, which are selectively activated by baclofen and CCGP27492 and are blocked by phaclofen, the phosphonic acid analogue of baclofen; hence, GABA B is found in central and peripheral nervous tissue 226 .…”

Section: ) Glutamatementioning

confidence: 99%

“…b) GABA receptors GABA is a highly flexible molecule and, thus, can exist in many low-energy conformations. Conformationally restricted analogues of GABA have been used to help identify three major GABA receptors, termed GABA A , GABA B and GABA C receptors [198][199][200] . GABA A and GABA C receptors are members of a superfamily of transmitter-gated ion channels that include nicotinic acetylcholine, strychninesensitive glycine and 5HT 3 receptors 201,203 .…”

Section: ) Glutamatementioning

confidence: 99%

See 1 more Smart Citation

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

View full text Add to dashboard Cite

Seventy years ago it was discovered that glutamate is abundant in the brain and that it plays a central role in brain metabolism. However, it took the scientific community a long time to realize that glutamate also acts as a neurotransmitter. Glutamate is an amino acid and brain tissue contains as much as 5 -15 mM glutamate per kg depending on the region, which is more than of any other amino acid. The main motivation for the ongoing research on glutamate is due to the role of glutamate in the signal transduction in the nervous systems of apparently all complex living organisms, including man. Glutamate is considered to be the major mediator of excitatory signals in the mammalian central nervous system and is involved in most aspects of normal brain function including cognition, memory and learning. In this review, the basic biology of the excitatory amino acids glutamate, glutamate receptors, GABA, and glycine will first be explored. In the second part of this review, the known pathophysiology and pathology will be described. (J Toxicol Pathol 2008; 21: 25-51)

show abstract

Section: ) Glutamatementioning

confidence: 99%

Section: ) Glutamatementioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

View full text Add to dashboard Cite

show abstract

“…Of the two known GABA receptor types -GABAA and GABAB [2] -only GABAA receptors have been found in these cells [3,6,8]. Binding of GABA to its receptors induces activation of C1-channels [2,3].…”

mentioning

confidence: 99%

“…Binding of GABA to its receptors induces activation of C1-channels [2,3]. The polarity of the membrane potential changes induced by a chloride current and, consequently, their effects on cell function depend critically upon the actual values of the resting membrane potential and the C1-equilibrium potential.…”

mentioning

confidence: 99%

γ-Aminobutyric acid elevates cytosolic Ca in bovine chromaffin cells

Doroshenko

1989

Neuroscience Letters

View full text Add to dashboard Cite

Measurements of the cytosolic Ca concentration ([Ca]i) with the Ca-sensitive dye, fura-2, showed that in intact, but not in voltage-clamped, bovine chromaffin cells ~,-aminobutyric acid (GABA, 10 pM) elicited a transient increase in [Ca]i. The Ca transient of intact cells was inhibited by bicuculline (20/~M), by removal of extracellular Ca or by treatment with the Ca channel blocker cobalt (2.5 mM), and enhanced by lowering the extracellular C1. We conclude, that GABA elevates [Ca]i by inducing a GABAA-receptorlinked C1 current which depolarizes the cell membrane sufficiently to activate potential-operated Ca channels and cause Ca entry into the cell.It is established that in chromaffin cells the primary determinant in secretion is an increase in intracellular Ca 2+ concentration [7,10]. Recent histochemical [1], biochemical [6, 8] and electrophysiological [3] studies showed that ~-aminobutyric acid (GABA) can modulate the function of the adrenal medulla. The mechanisms by which GABA influences secretion from chromaffin cells have not been established.Of the two known GABA receptor types -GABAA and GABAB [2] -only GABAA receptors have been found in these cells [3,6,8]. Binding of GABA to its receptors induces activation of C1-channels [2,3]. The polarity of the membrane potential changes induced by a chloride current and, consequently, their effects on cell function depend critically upon the actual values of the resting membrane potential and the C1-equilibrium potential. Because GABA stimulates catecholamine secretion from canine adrenal medulla [6] and cultured bovine chromaffin cells [8] in a Ca-dependent way, it has been deduced that GABA, like ACh, can depolarize the cells and elevate [Ca]i by opening potential-gated Ca channels.

show abstract

“…One complicating factor is the presence of HCO 3 Ϫ anions. The HCO 3 Ϫ permeability of the GABA A channel (Bormann, 1988;Fatima-Shad and Barry, 1993) impedes conclusions toward actual [Cl Ϫ ] i if they are calculated from reversal potentials of GABA A receptor-mediated anion currents. Furthermore, a HCO 3 Ϫ /Cl Ϫ exchanger (RaleySusman et al, 1993) may well interfere (Chesler, 1990), and pH changes that result from manipulations of [HCO 3 Ϫ ] o strongly affect neuronal excitability (Jarolimek et al, 1989;Chesler and Kaila, 1992).…”

mentioning

confidence: 99%

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

1999

View full text Add to dashboard Cite

Efficacy of postsynaptic inhibition through GABA A receptors in the mammalian brain depends on the maintenance of a Cl Ϫ gradient for hyperpolarizing Cl Ϫ currents. We have taken advantage of the reduced complexity under which Cl Ϫ regulation can be investigated in cultured neurons as opposed to neurons in other in vitro preparations of the mammalian brain. GABA is the main inhibitory transmitter in the mammalian brain. The dominant effect of GABA A receptor activation is a hyperpolarization caused by C l Ϫ flux into the cell (for review, see Sivilotti and Nistri, 1991;Kaila, 1994;Thompson, 1994). However, the direction of the C l Ϫ flux depends on the C l Ϫ gradient across the membrane. 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). To be able to predict the direction of C l Ϫ currents flowing during GABA A receptor-mediated inhibition it is essential to understand the regulation of C l Ϫ homeostasis that provides the transmembrane gradient.A recently cloned K ϩ -Cl Ϫ cotransporter gene (KCC2) represents a perfect candidate for the regulation of neuronal Cl Ϫ homeostasis (Payne et al., 1996). In contrast to the ubiquitous presence of the K ϩ -Cl Ϫ cotransporter KCC1, expression of the K ϩ -Cl Ϫ cotransporter KCC2 is detected in C NS only and seems to be neuron specific. KCC2 is also distinct from KCC1 in that KCC2 is not involved in cell volume regulation and not activated by osmotic changes. Furthermore, KCC2 has a high affinity for extracellular K ϩ ions. The properties of KCC2 allow the regulation of [Cl Ϫ ] i to maintain Cl Ϫ gradients for hyperpolarizing GABAergic inhibition. Thermodynamic considerations predict that the electroneutral K ϩ -Cl Ϫ cotransporter KCC2 operates near equilibrium under physiological ionic conditions. Depending on [Cl Ϫ ] i and [K ϩ ] o (Payne, 1997), the transport will extrude or accumulate Cl Ϫ .The functional role of a particular Cl Ϫ transport system in neuronal Cl Ϫ regulation is difficult to establish in studies using integral preparations such as brain slices. One complicating factor is the presence of HCO 3 Ϫ anions. The HCO 3 Ϫ permeability of the GABA A channel (Bormann, 1988;Fatima-Shad and Barry, 1993) impedes conclusions toward actual [Cl Ϫ ] i if they are calculated from reversal potentials of GABA A receptor-mediated anion currents. Furthermore, a HCO 3 Ϫ /Cl Ϫ exchanger (RaleySusman et al., 1993) may well interfere (Chesler, 1990), and pH changes that result from manipulations of [HCO 3 Ϫ ] o strongly affect neur...

show abstract

Electrophysiology of GABAA and GABAB receptor subtypes

Cited by 630 publications

References 35 publications

A Review of Glutamate Receptors I: Current Understanding of Their Biology

A Review of Glutamate Receptors I: Current Understanding of Their Biology

γ-Aminobutyric acid elevates cytosolic Ca in bovine chromaffin cells

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

Contact Info

Product

Resources

About

Electrophysiology of GABAA and GABAB receptor subtypes

Cited by 630 publications

References 35 publications

A Review of Glutamate Receptors I: Current Understanding of Their Biology

A Review of Glutamate Receptors I: Current Understanding of Their Biology

γ-Aminobutyric acid elevates cytosolic Ca in bovine chromaffin cells

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

Contact Info

Product

Resources

About

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