Functional heterogeneity of the "transporter" of electrogenic ionic pump of the Lumbricus terrestris somatic myocyte membrane.

Potential created by electrogenic ionic pumps under conditions of maximum activation in a warm standard ionic medium with K(+) after preincubation in cold potassium-free solution has two components: a higher ouabaine-insensitive "stationary" component, and a lower "regulatory" component sensitive to ouabaine, furosemide, and removal of Cl(-) or Ca(2+) from the medium. Functional heterogeneity of electrogenic ionic pumps is hypothesized implying the existence of two components: "stationary" (not regulated extracellularly) and "regulatory" (controlled and directly related to active Cl(-) transfer).

GABAergic function in Alzheimer's disease: evidence for dysfunction and potential as a therapeutic target for the treatment of behavioural and psychological symptoms of dementia.

Alzheimer's disease (AD) is characterized by disruptions in multiple major neurotransmitters. While many studies have attempted to establish whether GABA is disrupted in AD patients, findings have varied. We review evidence for disruptions in GABA among patients with AD and suggest that the variable findings reflect subtypes of the disease that are possibly manifested clinically by differing behavioural symptoms. GABA, the major inhibitory neurotransmitter, has long been a target for anxiolytics, hypnotic sedatives, and anticonvulsants. We review the clinical use of GABAergic agents in treating persons with AD symptoms. While newer generation GABAergic medications are now available, they have yet to be evaluated among patients with AD.

Recent advances in the GABA-A-benzodiazepine receptor pharmacology.

Gamma-aminobutyric acid (GABA) acts on pharmacologically and functionally distinct receptors. These sites designated GABA-A and GABA-B receptors, differ with regard to their ionic characteristic and pharmacological properties. The most important distinction is, that the GABA-A receptor is associated with chloride channel and with membrane recognition sites for benzodiazepines. During the past decade numerous studies have made it possible to obtain more detailed knowledge of the structure and properties of the GABA-benzodiazepine receptor complex, which is made up of at least two distinct sites designated as BZD-1 and BZD-2 receptors. Third type, designated as peripheral type is located in the mitochondrial membrane and may regulate a steroidogenesis in the CNS. Molecular cloning studies showed a heterogeneity of GABA-A receptors, which are composed of multiple subunits (alpha, beta, gamma, delta and ro), which form distinct isoreceptors. New classes of GABA-BZD agonists such as zolpidem act selectively upon certain isoreceptors thus showing characteristic pharmacological properties. Recent studies provided detailed information on the interaction of ethyl alcohol (Et-OH) with GABA-BZD receptor complex. The most important finding is, that there are Et-OH sensitive and Et-OH resistant GABA-A receptor isoforms. Recent evidence reinforces the possibility, that reduced activity of the brain GABA-ergic system is associated with mechanism of depression.