A5060721522- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Pain Mechanisms and Treatments
- Neuroendocrine regulation and behavior
- Ancient and Medieval Archaeology Studies
- Neural dynamics and brain function
- Ion Channels and Receptors
- Neuroscience of respiration and sleep
- Regulation of Appetite and Obesity
- Pharmacological Receptor Mechanisms and Effects
- Nicotinic Acetylcholine Receptors Study
- Influenza Virus Research Studies
- Steroid Chemistry and Biochemistry
- Material Properties and Applications
- Grief, Bereavement, and Mental Health
- Photoreceptor and optogenetics research
- Receptor Mechanisms and Signaling
- Barrier Structure and Function Studies
- Plant-based Medicinal Research
- Computational Drug Discovery Methods
- Electrolyte and hormonal disorders
- Digital Mental Health Interventions
- Hormonal Regulation and Hypertension
- Ion Transport and Channel Regulation
Linköping University
1991-2022
AstraZeneca (Sweden)
1993-2020
Umeå University
2008-2016
AstraZeneca (United Kingdom)
2002
University of Gothenburg
1989
The general lack of pain experience is a rare occurrence in humans, and the molecular causes for this phenotype are not well understood. Here we have studied Canadian family from Newfoundland with members who exhibit congenital inability to pain. We mapped locus 13.7 Mb region on chromosome 2q (2q24.3-2q31.1). Screening candidate genes identified protein-truncating mutation SCN9A, which encodes voltage-gated sodium channel Na(v)1.7. C-A transversion at nucleotide 984 transforming codon...
This study addresses the question of whether cholera toxin (CT) increases gut permeability for molecules > 3000 Da and such an effect is associated with adjuvant function by CT on immune response. We louiid that after oral administration gives rise to strikingly increased Dextran (Mw 3000) eoncomilantly a strong enhancing anti‐keyhole limpet heniocyanin (KLII) specific response in lamina propria immunization KLH plus CT. In contrast, B‐subunit hololoxin, which lacks adenylate...
Cholera toxin (CT) is a potent oral immunogen that also acts as strong mucosal adjuvant for immune responses to related well unrelated Ag. To elucidate the immunomodulating effects of CT at cellular level we have examined interactions with APC and B T lymphocytes in vitro. markedly stimulated production IL-1 from (mouse peritoneal macrophages or macrophage cell line P388D1) but did not induce Ia-Ag had marginal, if any, effect potentiating Ia Ag expression by rIFN-gamma on these cells....
Seventy monoclonal antibodies to cholera toxin were prepared and characterized. All of immunoglobulin G (IgG) isotypes (39 IgG1, 29 IgG2, 2 IgG3). A total 61 clones produced antibody directed against the B subunit, 9 with specificity for subunit. Among both anti-B anti-A antibodies, there representatives which showed full cross-reactivity heat-labile enterotoxin Escherichia coli (14 clones), others gave partial cross-reactions (12), still (44) did not cross-react. Although 24 25 tested could...
Allosteric communication pathways in the glucocorticoid receptor ligand-binding domain respond to ligand structure.
Studies of family reactions following teenage suicide are hampered by the psychological difficulties approaching families and recruiting an unbiased sample study subjects. By using a small but consecutive series cases, we examined qualitative aspects loosing member due to suicide. Such understanding is important for future organisation proper programs that provide professional support in grief process. From large project on unnatural death northern Sweden 1981–2000 (including 88 suicides),...
Desensitization of ligand-gated ion channels plays a critical role for the information transfer between neurons. The current view on γ-aminobutyric acid (GABA)(A) and glycine receptors includes significant rapid components desensitization as well cross-desensitization two receptor types. Here, we analyze mechanism apparent native GABA(A) in rat central neurons quantify to what extent decay presence ligand is result versus changes intracellular Cl(-) concentration ([Cl(-)](i)). We show that...
It is critical for survival to assign positive or negative valence salient stimuli in a correct manner. Accordingly, harmful and internal states characterized by perturbed homeostasis are accompanied discomfort, unease, aversion. Aversive signaling causes extensive suffering during chronic diseases, including inflammatory conditions, cancer, depression. Here, we investigated the role of melanocortin 4 receptors (MC4Rs) aversive processing using genetically modified mice behavioral test which...
Voltage-gated ion channels generate cellular excitability, cause diseases when mutated, and act as drug targets in hyperexcitability diseases, such epilepsy, cardiac arrhythmia pain. Unfortunately, many patients do not satisfactorily respond to the present-day drugs. We found that naturally occurring resin acid dehydroabietic (DHAA) is a potent opener of voltage-gated K channel thereby potential suppressor excitability. DHAA acts via non-traditional mechanism, by electrostatically activating...
Retigabine is unique among anticonvulsant drugs by targeting the neuronal M-channel, which composed of KV7.2/KV7.3 and contributes to negative resting membrane potential. Unfortunately, retigabine causes adverse effects, limits its clinical use. Adverse effects may be reduced developing M-channel activators with improved KV7 subtype selectivity. The aim this study was evaluate prospect endocannabinoids as activators, either in isolation or combined retigabine. Human channels were expressed...
Abstract Aim Polyunsaturated fatty acids have been reported to reduce neuronal excitability, in part by promoting inactivation of voltage‐gated sodium and calcium channels. Effects on potassium channels are less explored experimental data ambiguous. The aim this study was investigate anti‐excitable effects polyunsaturated the M‐channel, important for setting resting membrane potential hippocampal dorsal root ganglion neurones. Methods acid analogues mouse neurones human K V 7.2/3 channel...
1. Voltage-dependent Ca2+ channels triggering GABA release onto neurons from the medial preoptic nucleus of rat were investigated. Acutely dissociated with adherent functional synaptic terminals investigated by tight-seal whole-cell recordings postsynaptic cells. 2. Spontaneous current events similar to miniature currents recorded. They blocked bicuculline (100 microM), showed a roughly unimodal amplitude distribution and reversal potential consistent Cl- current, therefore attributed GABAA...
The relation between current and voltage, I-V relation, is central to functional analysis of membrane ion channels. A commonly used method, since the introduction voltage-clamp technique, establish depends on interpolation amplitudes recorded at different steady voltages. By a theoretical computational approach as well by experimental recordings from GABAA-receptor mediated currents in mammalian neurons, we here show that this method may give reversal potentials conductances do not reflect...
The accumulation of proteinaceous deposits comprised largely the α-synuclein protein is one main hallmarks Parkinson's disease (PD) and related synucleinopathies. Their progressive development coincides with site-specific phosphorylation, oxidative stress eventually, compromised neuronal function. However, modeling aggregate formation in animal or vitro models has proven notably difficult. Here, we took advantage a preclinical organotypic brain slice culture model to study ex vivo. We...
Abstract Objective About one third of all patients with epilepsy have pharmacoresistant seizures. Thus there is a need for better pharmacological treatments. The human voltage‐gated potassium (hK V ) channel hK 7.2/7.3 validated antiseizure target compounds that activate this channel. In previous study we shown resin acid derivatives can the investigated if these activators potential to be developed into new type drug. examined their structure‐activity relationships and site action on...