Cell Biochem Biophys
December 2024
Allopregnanolone (Allo) is a positive allosteric modulator of the GABA receptor, and amiloride (Ami) is a competitive antagonist of the GABA receptor. The purpose of this work was to study the combined effect of Allo and Ami on functional activity of GABA receptor. The GABA-induced chloride current (I) was measured in isolated Purkinje cells of rat cerebellum using the patch-clamp technique and a system of fast application.
View Article and Find Full Text PDFPicrotoxin (PTX), a convulsant of plant origin, has been used in many studies as research tool. PTX is the open channel blocker of the GABA receptor (GABAR). Being in the pore, PTX initiates transfer of the channel to the closed state and thus it falls into the "trap".
View Article and Find Full Text PDFACS Chem Neurosci
September 2023
The mechanism of the negative impact of corticosteroids on the induction and progress of mental illness remains unclear. In this work, we studied the effects of corticosteroids on the activity of neuronal glycine receptors (GlyR) and GABA-A receptors (GABAR) by measuring the chloride current induced by the application of GABA (2 or 5 μM) to isolated cerebellar Purkinje cells () and by the application of glycine (100 μM) to pyramidal neurons of the rat hippocampus (). It was found that corticosterone, 5α-dihydrodeoxycorticosterone, allotetrahydrocorticosterone, cortisol, and 17α,21-dihydroxypregnenolone were able to accelerate the desensitization of the at physiological concentrations (IC values varying from 0.
View Article and Find Full Text PDFγ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter. GABA receptor type A (GABAR) possesses binding sites for a large group of pharmacological agents which are supposed to interact allosterically with each other. The aim of this work was to study the interaction between the positive allosteric modulators (PAMs) and the competitive antagonists of GABARs.
View Article and Find Full Text PDFThe ability of endogenous neurosteroids (NSs) with pregnane skeleton modified at positions C-3 and C-5 to modulate the functional activity of inhibitory glycine receptors (GlyR) and ionotropic ɣ-aminobutyric acid receptors (GABA R) was estimated. The glycine and GABA-induced chloride current (I and I ) were measured in isolated pyramidal neurons of the rat hippocampus and in isolated rat cerebellar Purkinje cells, respectively. Our experiments demonstrated that pregnane NSs affected I and I in a different manner.
View Article and Find Full Text PDFThe ability of androstane and androstene neurosteroids with modifications at C-17, C-5, and C-3 (compounds -) to influence the functional activity of inhibitory glycine and γ-aminobutyric acid (GABA) receptors was estimated. The glycine- and GABA-induced chloride current ( and ) were measured in isolated pyramidal neurons of the rat hippocampus and isolated rat cerebellar Purkinje cells, correspondingly, using the patch-clamp technique. Our results demonstrate that all the nine neurosteroids display similar biological activity, namely, they strongly inhibited and weakly inhibited .
View Article and Find Full Text PDFThe ability of pregnanolone glutamate (PA-Glu), pregnanolone hemisuccinate (PA-hSuc) and pregnanolone hemipimelate (PA-hPim), neuroactive steroids with a negative modulatory effect on excitatory N-methyl-d-aspartate receptors, to influence the functional activity of inhibitory γ-aminobutyric acid and glycine receptors was estimated. The GABA- and glycine-induced chloride currents (I and I) were measured in isolated pyramidal neurons of the rat hippocampus using the patch-clamp technique. Compound PA-Glu was found to potentiate I and to inhibit I, while PA-hSuc and PA-hPim inhibited both I and I.
View Article and Find Full Text PDFHexafluoroisopropanol (HFIP) is a nonpolar organic solvent that is often used to prepare β-amyloid peptide (Aβ) samples. In this work, we compare the effects of two different species derived from synthetic Aβ1-42 and prepared without HFIP (Aβ) or using HFIP (Aβ/HFIP) on the glycine-activated chloride current (IGly). The experiments were conducted on the pyramidal neurons isolated from CA3 region of rat hippocampus.
View Article and Find Full Text PDFCyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are well known intracellular second messengers. At present study, we describe the effects of extracellularly applied cAMP and cGMP on glycine-induced chloride currents (I(Gly)) in isolated rat hippocampal pyramidal neurons. 50 or 500 μM glycine was applied for 600 ms with 1 min intervals.
View Article and Find Full Text PDFDonepezil is a cholinesterase inhibitor widely used for the treatment of Alzheimer's disease. Voltage-gated K(+)-channels are discussed as possible targets for the drug, but the results obtained by different authors are contradictory. In the present study performed on pyramidal cells isolated from rat's hippocampus, we investigated the effect of donepezil on delayed rectifier K(+)-current (I(K(DR))) and transient outward K(+)-current (I(K(A))) using patch-clamp technique.
View Article and Find Full Text PDFAcetylcholinesterase (AChE) inhibitor donepezil is widely used for the treatment of Alzheimer's disease (AD). The mechanisms of therapeutic effects of the drug are not well understood. The ability of donepezil to reverse a known pathogenic effect of β-amyloid peptide (Abeta), namely, the impairment of hippocampal long-term potentiation (LTP), was not studied yet.
View Article and Find Full Text PDFEarlier, we have shown a strong inhibitory effect of donepezil on K+-current of molluscan neurons (Solntseva et al., Comp Biochem Physiol 144, 319-326, 2007). In the present work, a possible interaction of donepezil with the external mouth of the channel was examined using, as a tool, tetraethylammonium (TEA), a classical antagonist of potassium channels.
View Article and Find Full Text PDFIn isolated neurons of Helix pomatia, a two-microelectrode voltage clamp technique was used to study the effect of Fe3+ on voltage-gated potassium currents: a low-threshold fast-inactivating current (I(A)) and a high threshold slow-inactivating current with calcium-dependent (I(C)) and calcium-independent (I(DR)) components. Extracellular application of FeCl3 rapidly, reversibly and dose-dependently reduced the amplitude of I(A), I(C) and I(DR) with IC50 values of 49, 45 and 70 microM, respectively. Complete inhibition of K+ currents was reached at 100-500 microM Fe3+.
View Article and Find Full Text PDFComp Biochem Physiol C Toxicol Pharmacol
January 2007
Donepezil is an acetylcholinesterase inhibitor used in Alzheimer's disease therapy. The neuroprotective effect of donepezil has been demonstrated in a number of different models of neurodegeneration including beta-amyloid toxicity. Since the mechanisms of neurodegeneration involve the activation of both Ca(2+)- and K(+)-channels, the study of donepezil action on voltage-gated ionic currents looked advisable.
View Article and Find Full Text PDF1. Literature data indicate that serotonin induces the long-term potentiation of glutamate (Glu) response in molluscan neurons. The aim of present work was to elucidate whether cyclic nucleotides can cause the same effect.
View Article and Find Full Text PDFInt J Neuropsychopharmacol
September 2002
The role of the voltage-gated K+ channels in the effect of some nootropics was investigated. Earlier, the multiple effect of high concentrations of two nootropics, piracetam and its peptide analogue GVS-111 [Seredenin et al. (1995), US Patent No.
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