Publications by authors named "Janna Kozuska"
Triton X-100 (TX-100) is a nonionic detergent frequently used at millimolar concentrations to disrupt cell membranes and solubilize proteins. At low micromolar concentrations, TX-100 has been reported to inhibit the function of potassium channels. Here, we have used electrophysiological and functional techniques to examine the effects of TX-100 on another class of ion channels, L-type voltage-operated calcium channels (VOCCs).
View Article and Find Full Text PDFPlastic consumables, used universally in bioscience laboratories, are presumed inert with respect to bioassay outcomes. However, it is clear that many pipette tips, microfuge tubes, and other plastic disposables leach bioactive compounds into assay solutions, profoundly affecting data and experimental interpretation. In this paper we discuss the nature and sources of leachates and review several examples of compromised bioassay data that speak to the probable widespread nature of this largely unrecognised source of error.
View Article and Find Full Text PDFThe Cys-loop pentameric ligand-gated ion channel receptors: 50 years on.
Can J Physiol Pharmacol
June 2012
Article Synopsis
- The Department of Pharmacology at the University of Alberta marked its 50th anniversary in 2011, coinciding with the history of research on Cys-loop pentameric ligand-gated ion channels (pLGICs).
- Major advancements in technology have significantly enhanced understanding of pLGICs, along with notable contributions from department members, particularly Susan Dunn.
- Dunn's innovative work in electrophysiological studies and her introduction of the 2-electrode voltage-clamp technique have influenced research on various receptors, highlighting her legacy in the field.
GABA is the major inhibitory neurotransmitter in the adult mammalian CNS. The ionotropic GABA type A receptors (GABA(A)Rs) belong to the Cys-loop family of receptors. Each member of the family is a large pentameric protein in which each subunit traverses the cell membrane four times.
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- The effects of benzodiazepines on GABA(A) receptors vary based on the specific α subunit isoform present, particularly α4 or α6 which typically make receptors insensitive to classical benzodiazepines.
- Researchers expressed the α4β3γ2L subtype in Xenopus oocytes and found that diazepam and flunitrazepam enhanced GABA-induced currents at low concentrations, similar to the more commonly responsive α1β2γ2 subtype.
- However, when α4β3γ2L receptors were expressed in HEK293 cells, traditional benzodiazepines showed low binding affinity and did not potentiate GABA currents, indicating the modulation effects are specific to the expression system used.
Cation-selective cysteine (Cys)-loop transmitter-gated ion channels provide an important pathway for Ca2+ entry into neurones. We examined the influence on Ca2+ permeation of amino acids located at intra- and extracellular ends of the conduction pathway of the human 5-hydroxytryptamine type 3A (5-HT3A) receptor. Mutation of cytoplasmic arginine residues 432, 436, and 440 to glutamine, aspartate, and alanine (the aligned residues of the human 5-HT3B subunit (yielding 5-HT3A(QDA)) increased PCa/PCs from 1.
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