A5018134952- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Ion Channels and Receptors
- Cardiac electrophysiology and arrhythmias
- Nitric Oxide and Endothelin Effects
- Ion Transport and Channel Regulation
- Neuroscience of respiration and sleep
- Heme Oxygenase-1 and Carbon Monoxide
- Genetic and Kidney Cyst Diseases
- Receptor Mechanisms and Signaling
- Connexins and lens biology
- Biomedical Research and Pathophysiology
- Sulfur Compounds in Biology
- Mitochondrial Function and Pathology
- Caveolin-1 and cellular processes
- Neonatal Health and Biochemistry
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Cardiac Ischemia and Reperfusion
- Renin-Angiotensin System Studies
- Eicosanoids and Hypertension Pharmacology
- Nicotinic Acetylcholine Receptors Study
- Cellular transport and secretion
- Phytochemicals and Antioxidant Activities
- Alcohol Consumption and Health Effects
- Renal and Vascular Pathologies
University of Tennessee Health Science Center
2015-2024
ORCID
2020
The University of Texas Health Science Center at Houston
2011
University of Memphis
2009
University of Chicago
2008
New York Medical College
2007
University of Vermont
1997-2000
University of Sheffield
1993-1995
Carbon monoxide (CO) is an endogenous paracrine and autocrine gaseous messenger that regulates physiological functions in a wide variety of tissues. CO induces vasodilation by activating arterial smooth muscle large-conductance Ca2+-activated potassium (BK(Ca)) channels. However, the mechanism which activates BK(Ca) channels remains unclear. Here, we tested hypothesis binding to channel-bound heme, channel inhibitor, altering interaction between heme conserved heme-binding domain (HBD) alpha...
Reactive oxygen species (ROS) can have divergent effects in cerebral and peripheral circulations. We found that Ca(2+)-permeable transient receptor potential ankyrin 1 (TRPA1) channels were present colocalized with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2), a major source ROS, the endothelium arteries but not other vascular beds. recorded characterized ROS-triggered Ca(2+) signals representing influx through single TRPA1 channels, which we called...
Rationale: Pressure-induced arterial depolarization and constriction (the myogenic response) is a smooth muscle cell (myocyte)-specific mechanism that controls regional organ blood flow systemic pressure. Several different nonselective cation channels contribute to pressure-induced depolarization, but signaling mechanisms involved are unclear. Similarly uncertain the contribution of anion response physiological functions regulation recently discovered transmembrane 16A (TMEM16A), also termed...
Carbon monoxide (CO) is generated endogenously by the enzyme heme oxygenase. Although CO a known vasodilator, cellular signaling mechanisms are poorly understood and source of controversy. The goal present study was to investigate dilation in porcine cerebral arterioles. Data indicate that exogenous or produced potent activator large-conductance Ca2+-activated K+ (K(Ca)) channels Ca2+ spark-induced transient K(Ca) currents arteriole smooth muscle cells. In contrast, relatively poor sparks....
1. The molecular nature of the strong inward rectifier K+ channel in vascular smooth muscle was explored by using isolated cell RT-PCR, cDNA cloning and expression techniques. 2. RT-PCR RNA from single cells rat cerebral (basilar), coronary mesenteric arteries revealed transcripts for Kir2.1. Transcripts Kir2.2 Kir2.3 were not found. 3. Quantitative PCR analysis significant differences transcript levels Kir2.1 between different preparations (n = 3; P < 0.05). A two-fold difference detected...
Ca 2+ sparks have been previously described in isolated smooth muscle cells. Here we present the first measurements of local transients (“Ca sparks”) an intact preparation. appear to result from opening ryanodine-sensitive release (RyR) channels sarcoplasmic reticulum (SR). Intracellular concentration ([Ca ] i ) was measured cerebral arteries (40–150 μm diameter) rats, using fluorescent indicator fluo 3 and a laser scanning confocal microscope. Membrane potential depolarization by elevation...
Mitochondria regulate intracellular calcium (Ca 2+ ) signals in smooth muscle cells, but mechanisms mediating these effects, and the functional relevance, are poorly understood. Similarly, antihypertensive ATP-sensitive potassium (K ATP channel openers (KCOs) activate plasma membrane K channels depolarize mitochondria several cell types, contribution of each to vasodilation is unclear. Here, we show that cerebral artery most effectively depolarized by diazoxide (−15%, tetramethylrhodamine...
Vasoconstrictors that bind to phospholipase C–coupled receptors elevate inositol-1,4,5-trisphosphate (IP 3 ). IP is generally considered intracellular Ca 2+ concentration ([Ca ] i ) in arterial myocytes and induce vasoconstriction via a single mechanism: by activating sarcoplasmic reticulum (SR)-localized receptors, leading release. We show also stimulates SR release–independent mechanism. In isolated cerebral artery arteries which was depleted abolish release (measured using D1ER,...
Transmembrane protein (TMEM)16A channels are recently discovered membrane proteins that display electrophysiological properties similar to classic Ca(2+)-activated Cl(-) (Cl(Ca)) in native cells. The molecular identity of generate Cl(Ca) currents smooth muscle cells (SMCs) resistance-size arteries is unclear. Similarly, whether cerebral artery SMCs controversial. Here, using biology and patch-clamp electrophysiology, we examined TMEM16A channel expression characterized arterial rat arteries....
Disruption of intestinal epithelial tight junctions is an important event in the pathogenesis ulcerative colitis. Dextran sodium sulfate (DSS) induces colitis mice with symptoms similar to However, mechanism DSS-induced unknown. We investigated disruption and barrier dysfunction Caco-2 cell monolayers vitro mouse colon vivo. DSS treatment resulted junctions, adherens actin cytoskeleton leading monolayers. induced a rapid activation c-Jun N-terminal kinase (JNK), inhibition or knockdown JNK2...
Ion channels composed of pore-forming and auxiliary subunits control physiological functions in virtually all cell types. A conventional view is that assemble with their before anterograde plasma membrane trafficking the protein complex. Whether multisubunit composition surface fixed following synthesis or flexible open to acute and, potentially, rapid modulation activity cellular excitability unclear. Arterial smooth muscle cells (myocytes) express large-conductance Ca(2+)-activated...
Key points Intravascular pressure is reported to activate several mechanosensitive ion channels, leading smooth muscle cell (SMC) depolarization, voltage‐dependent Ca 2+ channel activation and vasoconstriction; a process known as the ‘myogenic response’. Polycystin‐1 ‐2 (TRPP1 ‐2) have been shown differentially regulate mesenteric artery myogenic response, with TRPP2 expression attenuating vasoconstriction. We show that major TRPP isoform expressed located primarily in plasma membrane...
In arterial smooth muscle cells (myocytes), intravascular pressure stimulates membrane depolarization and vasoconstriction (the myogenic response). Ion channels proposed to mediate pressure-induced include several transient receptor potential (TRP) channels, including TRPM4, transmembrane protein 16A (TMEM16A), a Ca(2+) -activated Cl(-) channel (CaCC). 9-Phenanthrol, putative selective TRPM4 inhibitor, abolishes tone in cerebral arteries, suggesting that either is essential for...
Abstract TRPA1 is a Ca 2+ -permeable ion channel involved in many sensory disorders such as pain, itch and neuropathy. Notably, the function of depends on , with low potentiating high inactivating TRPA1. However, it remains unknown how exerts contrasting effects. Here, we show that regulates through calmodulin, which binds to -dependent manner. Calmodulin binding enhanced sensitivity -evoked potentiation at but inhibited promoted desensitization . inactivation were selectively prevented by...
Smooth muscle cell (myocyte) large-conductance calcium (Ca)(2+)-activated potassium (BK) channels are functionally significant modulators of arterial contractility. Arterial myocytes express both pore-forming BKα and auxiliary β1 subunits, which increase channel Ca(2+) sensitivity. Recently, several leucine-rich repeat containing (LRRC) proteins have been identified as γ subunits that elevate the voltage sensitivity recombinant prostate adenocarcinoma BK channels. LRRC expression...
Lymphatic collecting vessels exhibit spontaneous contractions with a pressure-dependent contraction frequency. The initiation of has been proposed to be mediated by the activity Ca2+-activated Cl- channel (CaCC). Here, we show that canonical CaCC Anoctamin 1 (Ano1, TMEM16a) plays an important role in lymphatic smooth muscle pacemaking. We find isolated murine cells express Ano1, and demonstrate functional currents can inhibited Ano1 inhibitor benzbromarone. These are absent from Cre...
Intestinal epithelial tight junction disruption is a primary contributing factor in alcohol-associated endotoxemia, systemic inflammation, and multiple organ damage. Ethanol acetaldehyde disrupt junctions by elevating intracellular Ca2+. Here we identify TRPV6, Ca2+-permeable channel, as responsible for alcohol-induced elevation of Ca2+, intestinal barrier dysfunction, inflammation. elicit TRPV6 ionic currents Caco-2 cells. Studies cell monolayers mouse organoids show that deficiency or...
Uridine 5′-triphosphate (UTP), a potent vasoconstrictor that activates phospholipase C, shifted Ca 2+ signaling from sparks to waves in the smooth muscle cells of rat cerebral arteries. UTP decreased frequency and transient -activated K + (K ) currents increased waves. The UTP-induced reduction spark did not reflect decrease global cytoplasmic , influx through voltage-dependent channels (VDCC), or load sarcoplasmic reticulum (SR), since was elevated, blocking VDCC prevent effect, SR...
The regulation of intracellular Ca 2+ signals in smooth muscle cells and arterial diameter by intravascular pressure was investigated rat cerebral arteries (∼150 μm) using a laser scanning confocal microscope the fluorescent indicator fluo 3. Elevation from 10 to 60 mmHg increased spark frequency 2.6-fold, wave 1.9-fold, global concentration ([Ca ] i ) 1.4-fold cells, constricted arteries. Ryanodine (10 μM), an inhibitor ryanodine-sensitive release channels, or thapsigargin (100 nM),...