A5001932915- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Nitric Oxide and Endothelin Effects
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Renin-Angiotensin System Studies
- Ion Channels and Receptors
- Neuroscience and Neural Engineering
- Neurobiology and Insect Physiology Research
- Adipose Tissue and Metabolism
- Cell Adhesion Molecules Research
- Nicotinic Acetylcholine Receptors Study
- Polyomavirus and related diseases
- Ion Transport and Channel Regulation
- Heat shock proteins research
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Mitochondrial Function and Pathology
- Photoreceptor and optogenetics research
- Fish Ecology and Management Studies
- Protein Structure and Dynamics
- Electrochemical Analysis and Applications
- Cardiac Ischemia and Reperfusion
- Phytochemicals and Antioxidant Activities
- Neuroinflammation and Neurodegeneration Mechanisms
University of Calgary
2016-2025
Libin Cardiovascular Institute of Alberta
2011-2025
MedStar Washington Hospital Center
2023
MedStar Health
2023
United States Air Force Research Laboratory
2022
Missouri Department of Conservation
2015-2016
Southeast Missouri State University
2016
Alberta Bible College
2012-2014
Alexandria University
2014
Institut de Mathématiques de Bordeaux
2014
The intracellular mechanism underlying the Ca(2+)-induced enhancement of L-type Ca2+ current (ICa) was examined in adult rabbit cardiac ventricular myocytes by using patch-clamp methodology. Internal elevated flash photolysis chelator Nitr 5, and levels were simultaneously monitored Fluo 3 fluorescence. Flash 5 produced a rapid (< 1-second) elevation internal Ca2+, which led to (39% 51% above control) peak inward after delay 20 120 seconds. dialysis with synthetic inhibitory peptides...
The multifunctional Ca++/calmodulin-dependent protein kinase II (CaM kinase) mediates Ca++-induced augmentation of L-type Ca++ current (ICa); therefore it may act as a proarrhythmic signaling molecule during early afterdepolarizations (EADs) due to ICa. To investigate the hypothesis that ICa-dependent EADs are favored by CaM activation were induced with clofilium in isolated rabbit hearts. All rapidly terminated ICa antagonists. Hearts pretreated inhibitor KN-93 or inactive analog KN-92 (0.5...
The contribution of small-conductance (SK Ca ) and intermediate-conductance 2+ -activated K + (IK channels to the generation nitric oxide (NO) by -mobilizing stimuli was investigated in human umbilical vein endothelial cells (HUVECs) combining single-cell microfluorimetry with perforated patch-clamp recordings monitor agonist-evoked NO synthesis, cytosolic transients, membrane hyperpolarization real time. ATP or histamine evoked reproducible elevations synthesis , as judged...
T-type (CaV3.1/CaV3.2) Ca(2+) channels are expressed in rat cerebral arterial smooth muscle. Although present, their functional significance remains uncertain with findings pointing to a variety of roles.This study tested whether CaV3.2 mediate negative feedback response by triggering sparks, discrete events that initiate hyperpolarization activating large-conductance Ca(2+)-activated K(+) channels.Micromolar Ni(2+), an agent selectively blocks but not CaV1.2/CaV3.1, was first shown...
L-type, voltage-gated Ca2+ channels (CaL) play critical roles in brain and muscle cell excitability. Here we show that currents through heterologously expressed neuronal smooth CaL channel isoforms are acutely potentiated following alpha5beta1 integrin activation. Only the alpha1C pore-forming subunit is for this process. Truncation site-directed mutagenesis strategies reveal regulation of Cav1.2 by requires phosphorylation C-terminal residues Ser1901 Tyr2122. These sites known to be...
Recent data have led us to hypothesize that selective activation of endothelial small- and/or intermediate-conductance, calcium-activated potassium channels (SK(Ca) and IK(Ca) channels, respectively) by the opener compounds NS309 DCEBIO would augment stimulated nitric oxide (NO) synthesis vasodilation in resistance arteries. Experimentally, ATP-evoked changes membrane potential, cytosolic Ca(2+), NO were recorded patch clamp microfluorimetry single human cells. Agonist-evoked inhibition...
Arteriolar myogenic vasoconstriction occurs when increased stretch or membrane tension leads to smooth muscle cell depolarization and opening of voltage-gated Ca2+ channels. To prevent positive feedback excessive pressure-induced vasoconstriction, studies in cerebral artery have suggested that activation large conductance, Ca2+-activated K+ channels (BKCa) provides an opposing hyperpolarizing influence reducing channel activity. We hypothesized this mechanism may not equally apply all...
Introduction Atherosclerosis remains a major risk factor for vascular dysfunction and cardiovascular (CV) disease. Pharmacological enhancement of endothelial Ca 2+ -activated K + channel activity (i.e., 2.3 3.1) opposes associated with ageing type 2 diabetes (T2D) in ex vivo preparations. In the current study, we have investigated efficacy this strategy to mitigate setting atherogenesis. Methods Male apolipoprotein E knockout (Apoe −/− ) mice fed high fat diet (HFD) were treated daily...
Breathing … it is one of the first and last things we do outside womb. Striated skeletal muscle comprises 30–40% total body mass generally considered a 'voluntary' as its movements are largely controlled consciously through central nervous system. An exception to this paradigm diaphragm, striated whose contractile activity drives inspiration by lowering intrapleural pressure, leading expansion lung parenchyma inhalation air. Rhythmic contractions diaphragm occur throughout our lifetime...
1. Activation of macroscopic membrane currents by intracellular calcium ([Ca2+]i) signalling pathways was examined in human T84 epithelial cells, a model secretory cell line. 2. Elevation [Ca2+]i either the ionophore A23187 (1 microM) or cholinergic agonist carbachol, led to transient activation both chloride and cation current single voltage clamped cells. The channels underlying conductance were found be equally permeable external Na+, K+ Cs+, but impermeable large organic cations...
1. Ventricular myocytes were isolated by enzymatic dispersion of adult rabbit hearts, and voltage clamped using the whole‐cell variation patch clamp technique. Experiments carried out at either 35 degrees C or room temperature (21‐23 C). 2. In presence 10(‐3) M‐4‐aminopyridine to block transient outward K+ current, 10(‐6) M‐propranolol beta‐adrenoceptors, alpha 1‐adrenergic agonist methoxamine produced action potential prolongation, a small depolarization diastolic membrane potential. Under...
1. The intracellular mechanism(s) underlying the decrease of a transient outward K+ current (It) induced by alpha 1‐adrenergic agonists was studied in isolated adult rabbit atrial myocytes using whole‐cell voltage clamp and cell‐attached patch techniques. Experiments were carried out at 22‐23 degrees C. 2. Application specific agonist, methoxamine, produced It which irreversible after non‐hydrolysable GTP analogues, gamma S Gpp(NH)p, had been introduced into cells via recording micropipette....
Injury/degradation of the extracellular matrix (ECM) is associated with vascular wall remodelling and impaired reactivity, a process in which altered ECM-integrin interactions play key roles. Previously, we found that peptides containing RGD integrin-binding sequence produce sustained vasodilatation rat skeletal muscle arterioles. Here, tested hypothesis ligands work through alpha5beta1 integrin to modulate activity large conductance, Ca(2+)-activated K(+) (BK) channels arteriolar smooth...
Abstract β1-Subunits enhance the gating properties of large-conductance Ca(2+)-activated K(+) channels (BKCa) formed by α-subunits. In arterial vascular smooth muscle cells (VSMCs), β1-subunits are vital in coupling SR-generated Ca(2+) sparks to BKCa activation, affecting contractility and blood pressure. Studies cremaster cerebral VSMCs show heterogeneity activity due apparent differences functional β1-subunit:α-subunit ratio. To define these differences, studies were conducted at...
Smooth muscle contractility and neuronal excitability are regulated by large conductance, Ca(2+)-activated K(+) (BKCa) channels, the activity of which can be increased after modulation type I cGMP-dependent protein kinase (cGKI) via nitric oxide (NO)/cGMP signaling. Our study focused on identifying key phosphorylation sites within BKCa channel underlying functional enhancement cGKI. cGKIα was characterized biochemically using radiolabeled ATP, regulation NO/cGMP signaling quantified in rat...
Elevated plasma glucose, as commonly seen in types I and II diabetes mellitus, is known to result endothelial dysfunction, a condition characterized by loss of nitric oxide (NO)-dependent regulation vascular tone. In the present study, we have utilized recently developed NO-sensitive fluorescent dye, DAF-FM (4-amino-5-methylamino-2′,7′-difluorofluorescein) diacetate directly examine consequences elevated glucose on agonist-evoked NO synthesis cultured human cells. Exposure cells for 5 7 days...