A5053934077- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- Cardiac Ischemia and Reperfusion
- Cardiovascular Function and Risk Factors
- Cardiomyopathy and Myosin Studies
- Polyamine Metabolism and Applications
- Cardiac Arrhythmias and Treatments
- Nicotinic Acetylcholine Receptors Study
- Photoreceptor and optogenetics research
- Electron Spin Resonance Studies
- Neurotransmitter Receptor Influence on Behavior
- Mechanical Circulatory Support Devices
- Cannabis and Cannabinoid Research
- Cardiovascular Effects of Exercise
- Nonlinear Dynamics and Pattern Formation
- Mass Spectrometry Techniques and Applications
- Electrochemical Analysis and Applications
- RNA and protein synthesis mechanisms
- Muscle Physiology and Disorders
- Cardiovascular Syncope and Autonomic Disorders
- bioluminescence and chemiluminescence research
- Cellular Mechanics and Interactions
- Neurological disorders and treatments
University of Michigan
2010-2023
Xavier University
2009
University of Massachusetts Amherst
2009
SUNY Upstate Medical University
2006
Washington University in St. Louis
1993-2003
Pennsylvania State University
2000
The mechanism of inward rectification was examined in cell-attached and inside-out membrane patches from Xenopus oocytes expressing the cloned strong rectifier HRK1. Little or no outward current measured patches. Inward currents reach their maximal value two steps: an instantaneous phase followed by a time-dependent "activation" phase, requiring at least exponentials to fit phase. After activating pulse, quasi-steady state current-voltage (I-V) relationship could be with single Boltzmann...
It has long been recognized that cationic nanoparticles induce cell membrane permeability. Recently, it found the formation and/or growth of nanoscale holes in supported lipid bilayers. In this paper, we show noncytotoxic concentrations 30−2000 pA currents 293A (human embryonic kidney) and KB epidermoid carcinoma) cells, consistent with a defect such as single hole or group ranging from 1 to 350 nm2 total area. Other forms defects, including nanoparticle porating agents adsorbing onto...
Previous studies have suggested an important role for the inward rectifier K + current ( I K1 ) in stabilizing rotors responsible ventricular tachycardia (VT) and fibrillation (VF). To test this hypothesis, we used a line of transgenic mice (TG) overexpressing Kir 2.1–green fluorescent protein (GFP) fusion cardiac‐specific manner. Optical mapping epicardial surface ventricles showed that Langendorff‐perfused TG hearts were able to sustain stable VT/VF 350 ± 1181 s at very high dominant...
A complementary DNA encoding an inward rectifier K+ channel (HRK1) was isolated from human hippocampus using a 392-base pair cDNA (HHCMD37) as probe.HRKl shows sequence similarity to three recently cloned inwardly rectifying potassium channels (IRK1, GIRKl, and ROMKl, 60, 42, 37%, respectively) has similar proposed topology of two membrane spanning domains that correspond the inner core structure voltage gated K' channels.When HRKl expressed in Xenopus oocytes, large currents were observed...
To assess the functional significance of upregulation cardiac current (IK1), we have produced and characterized first transgenic (TG) mouse model IK1 upregulation. increase density, a pore-forming subunit Kir2.1 (green fluorescent protein-tagged) channel was expressed in heart under control alpha-myosin heavy chain promoter. Two lines TG animals were established with high level expression all major parts heart: line 1 mice by 14% hypertrophy normal life span; 2 displayed an increased...
The effects of permeant (K+) ions on polyamine (PA)-induced rectification cloned strong inwardly rectifying channels (IRK1, Kir2.1) expressed in Xenopus oocytes were examined using patch-clamp techniques. kinetics PA-induced depend strongly external, but not internal, K+ concentration. Increasing external [K+] speeds up "activation" and shifts to more positive membrane potentials. shift is directly proportional the reversal potential (EK) with slope factors +0.62, +0.81, +0.91 for 1 mM...
Two different approaches were used to examine the in vivo role of polyamines causing inward rectification potassium channels. In two-microelectrode voltage-clamp experiments, 24-hr incubation Xenopus oocytes injected with 50 nl difluoromethylornithine (5 mM) and methylglyoxal bis(guanylhydrazone) (1 caused an approximate doubling expressed Kir2.1 currents relieved by approximately +10-mV shift voltage at which are half-maximally inhibited. Second, a putrescine auxotrophic, ornithine...
G protein-coupled receptors play a pivotal role in regulating cardiac automaticity. Their function is controlled by regulator of protein signaling (RGS) proteins acting as GTPase-activating for Galpha subunits to suppress Galpha(i) and Galpha(q) signaling. Using knock-in mice which Galpha(i2)-RGS binding negative regulation are disrupted genomic Galpha(i2)G184S (GS) point mutation, we recently (Fu Y, Huang X, Zhong H, Mortensen RM, D'Alecy LG, Neubig RR. Circ Res 98: 659-666, 2006) showed...
The molecular basis of G-protein inhibition inward rectifier K+ currents was examined by co-expression G-proteins and cloned Kir2 channel subunits in Xenopus oocytes. Channels encoded Kir2.3 (HRK1/HIR/BIRK2/BIR11) were completely suppressed with βγ subunits, whereas channels Kir2.1 (IRK1), which shares 60% amino acid identity Kir2.3, unaffected. Co-expression Gαi1 Gαq also partially currents, but Gαt, Gαs, a constitutively active mutant Gαil (Q204L) ineffective. Gβγ co-immunoprecipitated...
Loss-of-function (LOF) variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are linked to human diseases with high risk of sudden death, including developmental and epileptic encephalopathy cardiac arrhythmia. Subunits modulate the cell-surface localization, gating, kinetics pore-forming α subunits. They also participate cell-cell cell-matrix adhesion, resulting intracellular signal transduction, promotion cell migration, calcium handling, regulation morphology. Here, we...
Reducing the ATP sensitivity of sarcolemmal ATP-sensitive K(+) (K(ATP)) channel is predicted to lead active channels in normal metabolic conditions and hence cause shortened ventricular action potentials reduced myocardial inotropy. We generated transgenic (TG) mice that express an ATP-insensitive K(ATP) mutant [Kir6.2(deltaN2-30,K185Q)] under transcriptional control alpha-myosin heavy chain promoter. Strikingly, myocyte contraction amplitude was increased TG myocytes (15.68 +/- 1.15% vs....
Recent studies have shown that Kir2 channels display differential sensitivity to intracellular polyamines, and raised a number of questions about several properties inward rectification important the understanding their physiological roles. In this study, we carried out detailed characterization steady‐state kinetic block Kir2.1–3 by spermine. High‐resolution recordings from outside‐out patches showed in all current–voltage relationships ‘crossover’ effect upon change extracellular K + ....
Previous studies have shown that cardiac inward rectifier potassium current ( I K1 ) channels are heteromers of distinct Kir2 subunits and suggested species- tissue-dependent expression these may underlie variability . In this study, we investigated the contribution slowly activating Kir2.3 subunit free intracellular polyamines (PAs) to in mouse heart. The kinetics activation was measured concatemeric tetramers with known stoichiometry. Inclusion only one a Kir2.1 channel led an approximate...
Delayed rectifier potassium channels were expressed in the membrane of Xenopus oocytes by injection rat brain DRK1 (Kv2.1) cRNA, and currents measured cell-attached inside-out patch configurations. In intact cells current-voltage relationship displayed inward going rectification at potentials > +100 mV. Rectification was abolished excision patches into solutions containing no Mg2+ or Na+ ions, but restored introducing ions bath solution. At +50 mV, half-maximum blocking concentrations...