Large-conductance voltage and Ca super(2+)-activated potassium channels (BKCa) play a critical role in modulating contractile tone of smooth muscle, and neuronal processes. In most mammalian tissues, ...activation of beta -adrenergic receptors and protein kinase A (PKA sub(c)) increases BKCa channel activity, contributing to sympathetic nervous system/hormonal regulation of membrane excitability. Here we report the requirement of an association of the beta 2- adrenergic receptor ( beta 2AR) with the pore forming alpha subunit of BKCa and an A-kinase-anchoring protein (AKAP79/150) for beta 2 agonist regulation. beta 2AR can simultaneously interact with both BKCa and L-type Ca super(2+) channels (Ca sub(v)1.2) in vivo, which enables the assembly of a unique, highly localized signal transduction complex to mediate Ca super(2+)- and phosphorylation-dependent modulation of BKCa current. Our findings reveal a novel function for G protein-coupled receptors as a scaffold to couple two families of ion channels into a physical and functional signaling complex to modulate beta -adrenergic regulation of membrane excitability.
Large-conductance voltage and Ca2+-activated potassium channels (BKCa) play a critical role in modulating contractile tone of smooth muscle, and neuronal processes. In most mammalian tissues, ...activation of beta-adrenergic receptors and protein kinase A (PKAc) increases BKCa channel activity, contributing to sympathetic nervous system/hormonal regulation of membrane excitability. Here we report the requirement of an association of the beta2-adrenergic receptor (beta2AR) with the pore forming alpha subunit of BKCa and an A-kinase-anchoring protein (AKAP79/150) for beta2 agonist regulation. beta2AR can simultaneously interact with both BKCa and L-type Ca2+ channels (Cav1.2) in vivo, which enables the assembly of a unique, highly localized signal transduction complex to mediate Ca2+- and phosphorylation-dependent modulation of BKCa current. Our findings reveal a novel function for G protein-coupled receptors as a scaffold to couple two families of ion channels into a physical and functional signaling complex to modulate beta-adrenergic regulation of membrane excitability.
The amyloid beta peptide aggregates into amyloid plaques at presymptomatic stages of Alzheimer's disease, but the temporal relationship between plaque formation and neuronal dysfunction is poorly ...understood. Here we demonstrate that the connectivity of the peripheral olfactory neural circuit is perturbed in mice overexpressing human APPsw (Swedish mutation) before the onset of plaques. Expression of human APPsw exclusively in olfactory sensory neurons also perturbs connectivity with associated reductions in odour-evoked gene expression and olfactory acuity. By contrast, olfactory sensory neuron axons project correctly in mice overexpressing wild-type human amyloid precursor protein throughout the brain and in mice overexpressing M671V human APP, a missense mutation that reduces amyloid beta production, exclusively in olfactory sensory neurons. Furthermore, expression of Aβ40 or Aβ42 solely in the olfactory epithelium disrupts the olfactory sensory neuron axon targeting. Our data indicate that altering the structural connectivity and function of highly plastic neural circuits is one of the pleiotropic actions of soluble human amyloid beta.
Neuronal communications mediated by gaseous molecules like nitric oxide (NO) or carbon monoxide (CO) represent novel types of neurotransmission. NO and CO are synthesized by nitric oxide synthase ...(NOS) and heme oxygenase (HO), respectively. Both NO and CO can activate soluble guanylate cyclase (sGC) to increase cGMP levels. The present study used a combination of in vitro incubations and immunocytochemistry to examine the anatomical localization of HO and the biochemical and physiological effects of CO in the retina. The results indicated that HO-2, the constitutive isoform of HO, was present in many types of retinal neurons in turtle and several mammalian species. HO-2 was partially colocalized with sGC activity in turtle, and with neuronal NOS (nNOS) in many species. The physiological studies in turtle retina indicated that CO alone slightly increased cGMP levels in some bipolar and amacrine cells. CO also had an amplification effect on NO-induced increases in cGMP in many neurons. Surprisingly, NOS inhibitors were able to block all the CO stimulated increases in cGMP. Ultrastructural investigations in turtle retina indicated that nNOS could be diffusely localized in the cytoplasm, or it could be more selectively associated with the endoplasmic and nuclear membranes, and with some atypical and conventional mitochondria. In amacrine and bipolar cell synaptic terminals, nNOS was selectively localized at synaptic specializations. These results suggest that NO may play diverse roles in retinal neurons, and that NO may modulate synaptic activity at the level of single active zones. The present study provided the first localization of HO-2 in the retinas of many species. It also confirmed and extended the hypothesis that CO interacts with NO to modulate the NO/cGMP signal transduction pathway. The anatomical result correlates well with the widespread NO production found in previous NO imaging studies. Finally, the results imply that CO might be an intercellular and intracellular messenger in the retina, and that the interactions between CO and the NO/cGMP pathway may occur in the retinas of many species.
In view of the fact of the high concentration of neuronal nitric oxide synthase (NOS) in the supraoptic and paraventricular nuclei as well as the posterior pituitary, it has been supposed that nitric ...oxide (NO) may be involved in the regulation of hormone secretion from these sites. In the present study,
l-arginine, the precursor of NO, and
N
ω
-nitro-
l-arginine methyl ester (
l-NAME), the NOS inhibitor, were intracerebroventricularly (i.c.v.) administered into the pentobarbital anesthetized rats. The results showed that plasma arginine vasopressin (AVP) concentration increased after the injection of
l-arginine (1.0 mg in 10
μl, i.c.v.) and decreased after the
l-NAME (270
μg in 5
μl, i.c.v.). The elevated plasma AVP level in response to short-term hypotension induced by intravenous infusion of sodium nitroprusside was also significantly reduced by i.c.v. administration of
l-NAME. The results indicate that NO acts as a stimulating factor to both the basal and reflex release of AVP, opposing the view that NO plays an inhibitory role in the regulation of AVP secretion.
One of the few rules in ecology is that communities are composed of many rare and few common species. Trait‐based investigations of abundance distributions have generally focused on species‐mean ...trait values with mixed success. Here, using large tropical tree seedling datasets in China and Puerto Rico, we take an alternative approach that considers the magnitude of intraspecific variation in traits and growth as it relates to species abundance. We find that common species are less variable in their traits and growth. Common species also occupy core positions within community trait space indicating that they are finely tuned for the available conditions. Rare species are functionally peripheral and are likely transients struggling for success in the given environment. The work highlights the importance of considering intraspecific variation in trait‐based ecology and demonstrates asymmetry in the magnitude of intraspecific variation among species is critical for understanding of how traits are related to abundance.
This brief investigates the fixed-time containment control (FTCC) of second-order disturbed nonlinear multi-agent systems (MASs). A new nonsingular terminal sliding mode (NTSM) control protocol is ...devised to ensure the FTCC for disturbed nonlinear MASs. A novel NTSM surface is correspondingly proposed to ensure the fixed-time convergence of the considered systems. The explicit estimation of settling time is given as well, which is irrespective of system initial values. Finally, one numerical example is presented to demonstrate the correctness of the proposed results.
The PPC/PEO-hBN double-layer asymmetric electrolyte design provides close contact at the cathode interface and high mechanical strength at the Li metal anode, thus resulting in stable cycling ...performances in all-solid-state Li metal batteries.
Display omitted
All-solid-state Li metal battery has been regarded as a promising battery technology due to its high energy density based on the high capacity of lithium metal anode and high safety based on the all solid state electrolyte without inflammable solvent. However, challenges still exist mainly in the poor contact and unstable interface between electrolyte and electrodes. Herein, we demonstrate an asymmetric design of the composite polymer electrolyte with two different layers to overcome the interface issues at both the cathode and the anode side simultaneously. At the cathode side, the polypropylene carbonate layer has enough viscosity and flexibility to reduce the inter-facial resistance, while at the Li anode side, the polyethylene oxide layer modified with hexagonal boron nitride has high mechanical strength to suppress the Li dendrite growth. Owing to the synergetic effect between different components, the as-prepared double layer composite polymer electrolyte demonstrates a large electrochemical window of 5.17 V, a high ionic conductivity of 6.1 × 10−4 S/cm, and a transference number of 0.56, featuring excellent ion transport kinetics and good chemical stability. All-solid-state Li metal battery assembled with LiFePO4 cathode and Li anode delivers a high capacity of 150.9 mAh/g at 25 °C and 0.1 C-rate, showing great potential for practical applications.
PDF
