A5023839040- Ion Transport and Channel Regulation
- Renal Diseases and Glomerulopathies
- Sodium Intake and Health
- Ion channel regulation and function
- Chronic Kidney Disease and Diabetes
- Adenosine and Purinergic Signaling
- Renin-Angiotensin System Studies
- Nitric Oxide and Endothelin Effects
- Hormonal Regulation and Hypertension
- Neuroscience and Neuropharmacology Research
- Electrolyte and hormonal disorders
- Birth, Development, and Health
- Genetic and Kidney Cyst Diseases
- Gout, Hyperuricemia, Uric Acid
- Blood Pressure and Hypertension Studies
- Renal and related cancers
- Adolescent and Pediatric Healthcare
- Cardiac electrophysiology and arrhythmias
- Ion Channels and Receptors
- Metabolism and Genetic Disorders
- Circadian rhythm and melatonin
- Receptor Mechanisms and Signaling
- Metabolomics and Mass Spectrometry Studies
- Diet, Metabolism, and Disease
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
Medical University of South Carolina
2021-2025
Medical College of Wisconsin
2013-2022
ORCID
2020
Czech Academy of Sciences, Institute of Physiology
2016-2020
Cardiovascular Research Center
2020
University of Warwick
2009-2016
Google (United States)
2014
Bogomoletz Institute of Physiology
2012
University of Iowa
2008
Communication between neuronal and glial cells is important for many brain functions. Astrocytes can modulate synaptic strength via Ca(2+)-stimulated release of various gliotransmitters, including glutamate ATP. A physiological role ATP from astrocytes was suggested by its contribution to Ca(2+)-waves purinergic modulation activity sleep homeostasis. The mechanisms underlying gliotransmitters remain uncertain, exocytosis the most intriguing debated pathway. We investigated acutely...
The first point of our body’s contact with tactile stimuli (innocuous and noxious) is the epidermis, outermost layer skin that largely composed keratinocytes. Here, we sought to define role keratinocytes play in touch sensation vivo ex vivo. We show optogenetic inhibition decreases behavioral cellular mechanosensitivity. These processes are inherently mediated by ATP signaling, as demonstrated complementary cutaneous release degradation experiments. Specific deletion P2X4 receptors sensory...
Voltage-gated Nav channels are required for normal electrical activity in neurons, skeletal muscle, and cardiomyocytes. In the heart, Nav1.5 is predominant channel, Nav1.5-dependent regulates rapid upstroke of cardiac action potential. requires precise localization at specialized cardiomyocyte membrane domains. However, molecular mechanisms underlying channel trafficking heart unknown. this paper, we demonstrate that ankyrin-G targeting heart. Cardiomyocytes with reduced display expression,...
miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles both immune neuronal function. We describe here generation initial characterisation miR-132/212 double knockout mouse. These mice were viable fertile with no overt adverse phenotype. Analysis innate responses, including TLR-induced cytokine production IFNβ induction response viral infection primary fibroblasts did not reveal any phenotype...
Background Loss of glomerular podocytes is an indicator diabetic kidney disease (DKD). The damage to these cells has been attributed in part elevated intrarenal oxidative stress. primary source the renal reactive oxygen species, particularly H 2 O , NADPH oxidase 4 (NOX4). We hypothesized that NOX4-derived contributes podocyte DKD via elevation calcium. Methods used Dahl salt-sensitive (SS) rats with a null mutation for Nox4 gene (SS Nox4−/− ) and mice knockout nonselective calcium channel...
Abstract Injury to podocytes is considered a major contributor diabetic kidney disease: their loss causes proteinuria and progressive glomerulosclerosis. Podocyte depletion may result from improper calcium handling due abnormal activation of the permeant TRPC (Transient Receptor Potential Canonical) channels. Angiotensin II (Ang II) levels are found be elevated in diabetes; furthermore, it was reported that Ang TRPC6 podocytes. We hypothesized here II-mediated influx aggravated under...
Supplementing diets with high potassium helps reduce hypertension in humans. Inwardly rectifying K+ channels Kir4.1 (Kcnj10) and Kir5.1 (Kcnj16) are highly expressed the basolateral membrane of distal renal tubules contribute to Na+ reabsorption secretion through direct control transepithelial voltage. To define importance blood pressure under conditions salt-induced hypertension, we generated a Kcnj16 knockout Dahl salt-sensitive (SS) rats (SSKcnj16-/-). SSKcnj16-/- exhibited hypokalemia...
Abstract Recent studies highlighted the importance of astrocyte-secreted molecules, such as ATP, for slow modulation synaptic transmission in central neurones. Biophysical mechanisms underlying impact gliotransmitters on strength individual synapse remain, however, unclear. Here we show that purinergic P2X receptors can bring significant contribution to signalling boutons. ATP released from astrocytes facilitates a recruitment into excitatory synapses by Ca 2+ -dependent mechanism....
Significance Statement A novel disease phenotype comprises a tubulopathy with severe hypokalemia, renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness associated variants in KCNJ16 (K ir 5.1). In the kidney, inwardly rectifying potassium channel subunit forms functional heteromers KCNJ10 distal nephron KCNJ15 proximal tubule. Functional studies of mutant Xenopus oocytes demonstrate function complexes both KCNJ15. Individuals may present metabolic acidosis or...
Hypertension and kidney disease have been repeatedly associated with genomic variants alterations of lysine metabolism. Here, we combined stable isotope labeling untargeted metabolomics to investigate lysine's metabolic fate in vivo. Dietary 13C6 labeled was tracked metabolites across various organs. Globally, reacts rapidly molecules the central carbon metabolism, but incorporates slowly into proteins acylcarnitines. Lysine metabolism is accelerated a rat model hypertension damage, chiefly...
Astrocytes of the mouse neocortex express functional NMDA receptors, which are not blocked by Mg(2+) ions. However, pharmacological profile glial receptors and their subunit composition is far from complete.We tested sensitivity receptor-mediated currents to novel GluN2C/D subunit-selective antagonist UBP141 in cortical astrocytes neurons. We also examined effect memantine, an that has substantially different affinities for GluN2A/B GluN2C/d-containing physiological concentrations...
Cortical astrocytes express fast ionotropic receptors for glutamate and ATP, although their role in neurone-glia communication remains controversial. Stimulation of neuronal afferents mice neocortex triggers complex glial synaptic currents (GSCs) mediated by NMDA, P2X AMPA transporters. In addition, demonstrate spontaneous ‘miniature’ GSCs resulting from quantal release neurotransmitters. Here, we that maturation aging the brain (from 1 to 21 months) affect density generation. The...
Various stimuli, including hormones and growth factors, modulate epithelial sodium channels (ENaCs), which fine-tune Na(+) absorption in the kidney. Members of EGF family are important for maintaining transepithelial transport, but whether influences ENaC, perhaps mediating salt-sensitive hypertension, is not well understood. Here, ENaC inhibitor benzamil attenuated development hypertension Dahl rats. Feeding these rats a high-salt diet led to lower levels kidney cortex enhanced expression...
Diabetic kidney disease (DKD) is a chronic pathology that leads to end-stage renal disease. Previous studies from our laboratory indicate there an association between the development of DKD and transient receptor potential canonical 6 (TRPC6) channel. Trpc6 expression activity were increased in streptozotocin (STZ)-treated Dahl Salt-sensitive (Dahl SS) rat, established model type 1 diabetes. Here, using knockout created on SS rat background (SSTrpc6-/-), we test hypothesis absence will...
Hypertension is a persistent epidemic across the developed world that closely associated with kidney disease. Here, we applied metabolomic, phosphoproteomic, and proteomic strategy to analyze effect of hypertensive insults on kidneys. Our data revealed metabolic aspects hypertension-induced glomerular sclerosis, including lipid breakdown at early disease stages activation anaplerotic pathways regenerate energy equivalents counter stress. For example, branched-chain amino acids proline,...
The present study indicates that Na + -glucose cotransporter-2 (SGLT2) inhibition in a nondiabetic model of salt-sensitive hypertension blunts the development and magnitude salt-induced hypertension. Chronic SGLT2 increases glucose excretion without secondary effects on expression function other transporters channels along nephron hormone levels renin-angiotensin-aldosterone system. These data provide novel insights into inhibitors their potential use
Cardiac sodium channels (voltage-gated Na + channel subunit 1.5) reside in both the plasmalemma and membrane invaginations called caveolae. Opening of caveolar neck permits resident to become functional. In cardiac myocytes, opening can be stimulated by applying β-receptor agonists, which initiates an interaction between stimulatory G protein subunit-α (G s α) caveolin-3. This study shows that, adult rat ventricular a functional α-caveolin-3 occurs, even absence caveolin-binding sequence...
The ability of neurons to modulate synaptic strength underpins plasticity, learning and memory, adaptation sensory experience. Despite the importance in directing, reinforcing, revising behavioral response environmental influences, cellular molecular mechanisms underlying are far from clear. Brain-derived neurotrophic factor (BDNF) is a prime initiator structural functional adaptation. However, signaling cascade activated by BDNF initiate these adaptive changes has not been elucidated. We...
Communication between neuronal and glial cells is thought to be very important for many brain functions. Acting via release of gliotransmitters, astrocytes can modulate synaptic strength. The mechanisms underlying ATP from remain uncertain with exocytosis being the most intriguing debated pathway. We have demonstrated that d-serine released cortical in situ by a SNARE-complex-dependent mechanism. Exocytosis activate post-synaptic P2X receptors adjacent neurons, causing downregulation...
Abstract The interplay between long-term potentiation and depression (LTD) is thought to be involved in learning memory formation. One form of LTD expressed the hippocampus initiated by activation group 1 metabotropic glutamate receptors (mGluRs). Importantly, mGluRs have been shown critical for acquisition new memories reversal learning, processes that are crucial cognitive flexibility. Here we provide evidence MAPK-activated protein kinases 2 3 (MK2/3) regulate neuronal spine morphology,...