A5004271534- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Neuroscience and Neural Engineering
- Calcium signaling and nucleotide metabolism
- Phosphodiesterase function and regulation
- Nicotinic Acetylcholine Receptors Study
- Ion Channels and Receptors
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Genetics and Neurodevelopmental Disorders
- Metabolism and Genetic Disorders
- Medical Imaging and Analysis
- Diet and metabolism studies
- Pregnancy and preeclampsia studies
- Plant and Biological Electrophysiology Studies
- Spine and Intervertebral Disc Pathology
- Venomous Animal Envenomation and Studies
- Bone Tumor Diagnosis and Treatments
- Aortic aneurysm repair treatments
- Neuroendocrine regulation and behavior
- Pancreatic function and diabetes
- Neuropeptides and Animal Physiology
- PARP inhibition in cancer therapy
University of California, Irvine
2011-2023
Oregon Health & Science University
2003-2008
Vollum Institute
2003-2008
Howard Hughes Medical Institute
2003-2008
Kanazawa University
1997-2006
Akita University
1996-2002
Google (United States)
1995
Gifu University
1992
A-Kinase Anchoring Proteins (AKAPs) ensure the fidelity of second messenger signaling events by directing protein kinases and phosphatases toward their preferred substrates. AKAP150 brings kinase A (PKA), calcium/calmodulin dependent phosphatase PP2B C (PKC) to postsynaptic membranes where they facilitate phosphorylation modulation certain ion channels. Immunofluorescence electrophysiological recordings were combined with behavioral analyses assess whether removal gene targeting in mice...
Compartmentalization of the cAMP-dependent protein kinase (PKA) is coordinated through association with A-kinase anchoring proteins (AKAPs). A defining characteristic most AKAPs a 14- to 18-aa sequence that binds regulatory subunits (RI or RII) kinase. Cellular delivery peptides these regions disrupts PKA and has been used delineate physiological role for in facilitation certain cAMP-responsive events. Here, we describe bioinformatic approach yields an RII-selective peptide, called AKAP-...
Control of specificity in cAMP signaling is achieved by A-kinase anchoring proteins (AKAPs), which assemble effectors such as protein kinase A (PKA) into multiprotein complexes the cell. AKAPs tether PKA holoenzymes at subcellular locations to favor phosphorylation selected substrates. mediated an amphipathic helix 14-18 residues on each AKAP that binds R subunit dimer holoenzymes. Using a combination bioinformatics and peptide array screening, we have developed high affinity-binding called...
M-channel inhibitors, especially XE991, are being used increasingly in animal experiments; however, insufficient characterization of XE991 at times confounds the interpretation results when using this compound. Here, we demonstrate that and linopirdine state-dependent inhibitors favor activated-subunit neuronal Kv7/KCNQ channels. We performed patch-clamp experiments on homomeric Kv7.2 or heteromeric Kv7.2/3 channels expressed Chinese hamster ovary cells to characterize linopirdine. Neither...
Voltage-gated sodium (Na V ) and potassium (K channels are critical components of neuronal action potential generation propagation. Here, we report that Na β1 encoded by SCN1b , an integral subunit channels, coassembles with modulates the biophysical properties K 1 7 but not 3 in isoform-specific manner. Distinct domains involved modulation different channels. Studies channel chimeras demonstrate β1-mediated changes activation kinetics voltage dependence require interaction channel’s...
All subtypes of KCNQ channel subunits (KCNQ1-5) require calmodulin as a co-factor for functional channels. It has been demonstrated that plays critical role in trafficking well calcium-mediated current modulation. However, how calcium-bound suppresses the M-current is not understood. In this study, we investigated molecular mechanism KCNQ2 suppression mediated by calmodulin. We show calcium induced slow dissociation from subunit. contrast, homomeric KCNQ3 channels, facilitated binding....
Valproic acid (VPA) has been widely used for decades to treat epilepsy; however, its mechanism of action remains poorly understood. Here, we report that the anticonvulsant effects nonacute VPA treatment involve preservation M-current, a low-threshold noninactivating potassium current, during seizures. In wide variety neurons, activation Gq-coupled receptors, such as m1 muscarinic acetylcholine receptor, suppresses M-current and induces hyperexcitability. We demonstrated disrupts suppression...
Significance Dissemination of chemical information throughout the cell is a fundamental biological process with clinical relevance. Pathological changes in local signaling enzyme activity are linked to diseases, including schizophrenia, Alzheimer’s disease, cardiac arrhythmias, and seizures. Mining patient datasets has uncovered genetic variation A-kinase anchoring proteins (AKAPs) that promotes mislocalization protein kinase A (PKA). We investigate 42 SNPs AKAPs interrupt association PKA...
Cerebellar granule neurons possess a non-inactivating K+ current, which controls resting membrane potentials and modulates the firing rate by means of muscarinic agonists. kcr1 was cloned from cerebellar cDNA library suppression cloning. KCR1 is novel protein with 12 putative transmembrane domains enhances functional expression current in Xenopus oocytes. also accelerates activation rat EAG channels expressed oocytes or COS-7 cells. Far-Western blotting revealed that proteins interacted each...
Patients with LQTS (long QT syndrome) a mutation in cardiac ion channel gene, leading to mild-to-moderate dysfunction, may manifest marked prolongation or torsade de pointes only upon an additional stressor. A 59-year-old woman had and repeated 3 months after initiation of probucol, cholesterol-lowering drug. We identified single base substitution the HERG gene by genetic analysis. This novel missense is predicted cause amino acid Met(124)-->Thr (M124T) N-terminus. Three other relatives this...
Summary Objectives The M‐current is a low‐threshold voltage‐gated potassium current generated by Kv7 subunits that regulates neural excitation. It important to note suppression, induced activation of Gq‐coupled neurotransmitter receptors, can dynamically regulate the threshold action‐potential firing and frequency. Here we sought directly examine whether suppression involved in seizures epileptogenesis. Methods Kv7.2 knock‐in mice lacking key protein kinase C (PKC) phosphorylation acceptor...
Extracellular application of the novel brain peptides endomorphin 1 (EM1) and 2 (EM2) inhibited high‐threshold Ca 2+ channel currents in NGMO‐251 cells, a daughter clone NG108‐15 mouse neuroblastoma × rat glioma hybrid which μ‐opioid receptors are overexpressed. In contrast, EM1 EM2 did not induce this inhibition parental cells that predominantly express endogenous δ‐receptors. The IC 50 for was 7.7 23.1 n m , respectively. EM‐induced current blocked by treatment or pretreatment with 100 μ N...