Abstract —Compartmentalization of cAMP-dependent protein kinase A (PKA) by A-kinase anchoring proteins (AKAPs) targets PKA to distinct subcellular locations in many cell types. However, the question whether AKAP-mediated heart regulates cardiac contractile function has not been addressed. We disrupted myocytes introducing, via adenovirus-mediated gene transfer, Ht31, a peptide that binds regulatory subunit type II (RII) with high affinity. This competes endogenous AKAPs for RII binding....

Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) and vanilloid (TRPV1) are structurally related, non-selective cation that show a high permeability to calcium. Previous studies indicate TRP play prominent role in regulation cardiovascular dynamics homeostasis, but also contribute pathophysiology many diseases disorders within system. However, no date have identified functional expression and/or intracellular localization TRPA1 primary adult mouse ventricular...

Antibodies to the beta1-adrenergic receptor (beta1AR) are detected in a substantial number of patients with idiopathic dilated cardiomyopathy (DCM). The mechanism whereby these autoantibodies exert their pathogenic effect is unknown. Here, we define causal beta1AR-specific mediate noninflammatory cardiomyocyte cell death during murine DCM.We used beta1AR protein as an immunogen SWXJ mice and generated polyclonal battery that showed selective binding beta1AR. After transfer into naive male...

We have previously shown transient receptor potential vanilloid subtype 1 (TRPV1) channel-dependent coronary function is compromised in pigs with metabolic syndrome (MetS). However, the mechanisms through which TRPV1 channels couple blood flow to metabolism are not fully understood. employed mice lacking [TRPV1((-/-))], db/db diabetic, and control C57BKS/J determine extent modulate contribute vascular dysfunction diabetic cardiomyopathy. Animals were subjected vivo infusion of agonist...

Significance Endothelial cell migration is required for vessel repair after damage during angioplasty. Migration inhibited by lipid oxidation products, including lysophosphatidylcholine (lysoPC), that are abundant in atherosclerotic plaques. Inhibition of dependent on Ca 2+ entering through canonical transient receptor potential 6 (TRPC6) channels externalized lysoPC's action. Here we uncover an unappreciated role activation PI3K calmodulin (CaM) requiring phosphorylation its Tyr 99 ....

Recent studies have suggested a central role for Ca²⁺ in the signaling pathway of apoptosis and certain anti-apoptotic effects Bcl-2 family proteins been attributed to changes intracellular homeostasis. Here we report that depletion from endoplasmic reticulum (ER) leads Chinese hamster ovary cells. Stable expression ryanodine receptor (RyR) these cells enables rapid reversible both cytosolic ER content via activation RyR/Ca²⁺release channel by caffeine ryanodine....

The release of arachidonic acid by phospholipases in response to cell surface receptor activation may be an important step the initiation inotropic events cardiac muscle. Endothelin has been shown activate phospholipase A2 and isolated rat hearts. also a positive effect muscle, suggesting that endothelin increases Ca2+ influx or amount released from sarcoplasmic reticulum. We used suspensions adult ventricular myocytes loaded with fura-2/AM compare effects on transients evoked extracellular...

Essential oils were obtained by hydrodistillation of the umbels+seeds and stems Ferula akitschkensis (FAEOu/s FAEOstm, respectively) analyzed gas chromatography chromatography-mass spectrometry. Fifty-two compounds identified in FAEOu/s; primary components sabinene, α-pinene, β-pinene, terpinen-4-ol, eremophilene, 2-himachalen-7-ol, whereas FAEOstm myristicin geranylacetone. FAEOu/s, γ-terpinene, geranylacetone, isobornyl acetate, (E)-2-nonenal stimulated [Ca(2+)]i mobilization human...

Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation that show high permeability to calcium. Previous studies from our laboratory have demonstrated TRPA1 ion expressed in adult mouse ventricular cardiomyocytes (CMs) and localized at z-disk, costamere intercalated disk. The functional significance modulation CM contractile function not been explored.To identify extent which involved modulating elucidate cellular mechanism action.Freshly isolated CMs...

Background The cellular mechanisms that mediate the cardiodepressant effects of intravenous anesthetic agents remain undefined. objective this study was to elucidate direct propofol and ketamine on cardiac excitation-contraction coupling by simultaneously measuring intracellular calcium concentration ([Ca2+]i) shortening in individual, field-stimulated ventricular myocytes. Methods Freshly isolated rat myocytes were loaded with Ca2+ indicator, fura-2, placed stage an inverted fluorescence...

Objective— Endothelial cell (EC) migration, essential for reestablishing arterial integrity after vascular injury, is inhibited by oxidized LDL (oxLDL) and lysophosphatidylcholine (lysoPC) that are present in the wall. We tested hypothesis a mechanism responsible lysoPC-induced inhibition increased intracellular free calcium concentration ([Ca 2+ ] i ). Methods Results— LysoPC, at concentrations inhibit vitro EC migration to 35% of control, [Ca levels 3-fold. These effects lysoPC were...

Protein kinase A anchoring proteins (AKAPs) tether cAMP-dependent protein (PKA) to specific subcellular locations. The muscle AKAP, mAKAP, co-localizes with the sarcoplasmic reticulum Ca2+ release channel or ryanodine receptor (RyR). purpose of this study was determine whether PKA by mAKAP regulates RyR function. Either mAKAP-P, which is unable anchor PKA, expressed in CHO cells stably expressing skeletal isoform (CHO-RyR1). Immunoelectron microscopy showed that co-localized RyR1 disrupted...

Little is known about the pharmacological activity of Monarda fistulosa L. essential oils. To address this issue, we isolated oils from flowers and leaves M. analyzed their chemical composition. We also effects on transient receptor potential (TRP) channel activity, as these channels are targets various oil constituents. Flower (MEOFl) leaf (MEOLv) were comprised mainly monoterpenes (43.1% 21.1%) oxygenated (54.8% 77.7%), respectively, with a high abundance monoterpene hydrocarbons,...

Effectors involved in G protein-coupled receptor signaling modulate activity of GTPases through GTPase-activating protein or guanine nucleotide exchanging factor (GEF). Phospholipase Cdelta1 (PLCdelta1) is an effector tissue transglutaminase (TGII)-mediated alpha1B-adrenoreceptor (alpha(1B)AR) signaling. We investigated whether PLCdelta1 modulates TGII activity. stimulated GDP release from a concentration-dependent manner, resulting increase GTPgammaS binding to TGII. also inhibited GTP...

It is believed that inotropic agents exert their effects in cardiac muscle via a modulation of Ca2+ cycling; however, the involvement phospholipase activation and biochemical pathways participating responsiveness remain unclear. The aim current study was to determine whether arachidonic acid and/or eicosanoids participate responses by modulating cycling myocytes. Experiments were performed with populations freshly isolated, fura-2-loaded adult rat ventricular Arachidonic stimulated transient...

Abstract Essential oil extracts from Ferula iliensis have been used traditionally in Kazakhstan for treatment of inflammation and other illnesses. Because little is known about the biologic activity these essential oils that contributes to their therapeutic properties, we analyzed chemical composition evaluated phagocyte immunomodulatory activity. The main components extracted were (E)-propenyl sec-butyl disulfide (15.7–39.4%) (Z)-propenyl (23.4–45.0%). stimulated [Ca2+]i mobilization human...

We have reported that pretreatment with the clinically approved superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), blunts cardiorespiratory depressant responses elicited by a subsequent injection of fentanyl, in halothane-anesthetized rats. The objective present study was to determine whether is able reverse effects morphine on arterial blood-gas (ABG) chemistry freely-moving Sprague Dawley intravenous (10 mg/kg) substantial decreases pH, pO 2 and sO were...

The objectives were to determine the extent and mechanism of action by which propofol increases myofilament Ca2+ sensitivity intracellular pH (pHi) in ventricular myocytes.Freshly isolated adult rat myocytes used for study. Cardiac myofibrils extracted assessment myofibrillar actomyosin adenosine triphosphatase (ATPase) activity. Myocyte shortening (video edge detection) pHi (2',7'-bis-(2-carboxyethyl)-5(6')-carboxyfluorescein, 500/440 ratio) monitored simultaneously individual cells...

Abstract Modulation of [Ca 2+ ] i in response to receptor activation is a critical determinant vascular smooth muscle tone. In this study, we examined the effect continuous stimulation α 1 -adrenoceptors with phenylephrine (PE) on single pulmonary artery cells (PASMCs) cultured from explants canine intrapulmonary artery. Fura 2–loaded PASMCs pretreated propranolol (5 μmol/L) were continuously superfused PE at 37°C stage an inverted fluorescence microscope, and was measured using...

Recent evidence has suggested that arachidonic acid (AA) may be an important signaling molecule in cardiac excitation-contraction coupling. We previously showed AA and endothelin-1 (ET) inhibit distinct K+ channels via protein kinase C-dependent pathways rat ventricular myocytes. In addition, we demonstrated Ca2+ transients populations of fura 2-loaded myocytes were potentiated by ET activation C. this study, have used suspensions [32P]orthophosphate (32Pi)-labeled to study the effects at...

Background Activation of beta adrenoreceptors by catecholamines is an important mechanism for increasing the inotropic state heart. The objectives current study were to investigate effects propofol on beta-adrenoreceptor-mediated increases in cardiomyocyte intracellular Ca2+ concentration ([Ca2+]i), cell shortening, L-type (ICa) and cyclic adenosine monophosphate (cAMP) accumulation. authors also investigated site action beta-adrenoreceptor signaling pathway, as well role protein kinase C...

Introduction: Despite their inclination to induce tolerance, addictive states, and respiratory depression, synthetic opioids are among the most effective clinically administered drugs treat severe acute/chronic pain surgical anesthesia. Current medical interventions for opioid-induced depression (OIRD), wooden chest syndrome, opioid use disorder (OUD) show limited efficacy marked by low success in face of highly potent such as fentanyl. D-Cysteine ethylester (D-CYSee) prevents OIRD...