Blockade of acetylcholine release by botulinum neurotoxin type A at the neuromuscular junction induces formation an extensive network nerve-terminal sprouts. By repeated in vivo imaging N -(3-triethyl ammonium propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide uptake into identified nerve endings mouse sternomastoid muscle after a single intramuscular injection toxin, inhibition stimulated dye terminals was detected within few days, together with increase staining newly formed After 28...

Seven types (A-G) of botulinum neurotoxin (BoNT) target peripheral cholinergic neurons where they selectively proteolyze SNAP-25 (BoNT/A, BoNT/C1, and BoNT/E), syntaxin1 (BoNT/C1), synaptobrevin (BoNT/B, BoNT/D, BoNT/F, BoNT/G), SNARE proteins responsible for transmitter release, to cause neuromuscular paralysis but different durations. BoNT/A lasts longest (4-6 months) in humans, hence its widespread clinical use the treatment dystonias. Molecular mechanisms underlying these distinct...

Tetanus toxin (100 nM) when preincubated with guinea pig cerebrocortical synaptosomes for 45 min reduces the final extent of KCl-evoked, Ca(2+)-dependent, glutamate transmitter release to 30% non-intoxicated controls. Similarly, 100 nM Botulinum neurotoxins, types A and B, 90 inhibit 45-60% The toxins preferentially attenuate a slow phase KCl-evoked which may be associated synaptic vesicle mobilization. additionally inhibits aspartate, gamma-aminobutyric acid met-enkephalin from same...

Calcitonin-gene-related peptide (CGRP), a potent vasodilator that mediates inflammatory pain, is elevated in migraine; nevertheless, little known about its release from sensory neurons. In this study, CGRP was found to occur the majority of neurons rat trigeminal ganglia, together with three exocytotic SNAREs [SNAP25, syntaxin 1 and synaptobrevin (Sbr, also as VAMP) isoforms] synaptotagmin. Ca(2+)-dependent evoked K(+)-depolarisation and, lower levels, by capsaicin or bradykinin contain...

The seven types (A−G) of botulinum neurotoxin (BoNT) are Zn2+-dependent endoproteases that potently block neurosecretion. Syntaxin is presently thought to be the sole substrate for BoNT/C1, and synaptosomal-associated protein Mr = 25 000 (SNAP-25) selectively proteolyzed by A E. In this study, effects C1 on Ca2+-regulated exocytosis dense core granules from adreno-chromaffin cells were examined together with its underlying molecular action. Intact chromaffin exposed toxin, catecholamine...

Using pharmacological (Simpson, L.L., 1980, J. Pharmacol. Exp. Ther. 212:16-21) and autoradiographic techniques (Black, J.D., J.O. Dolly, 1986, Cell Biol., 103:521-534), it has been shown that botulinum neurotoxin (BoNT) is translocated across the motor nerve terminal membrane to reach a postulated intraterminal target. In present study, nature of this uptake process was investigated using electron microscopic autoradiography. It found internalization acceptor-mediated binding specific cell...

Excessive release of inflammatory/pain mediators from peripheral sensory afferents renders nerve endings hyper-responsive, causing central sensitization and chronic pain. Herein, the basal proinflammatory calcitonin gene-related peptide (CGRP) was shown to increase excitability trigeminal neurons in brainstem slices via CGRP1 receptors because effect negated by an antagonist, CGRP8–37. This excitatory action could be prevented cleaving synaptosomal-associated protein M r 25,000 (SNAP-25)...

The labeling patterns produced by radioiodinated botulinum neurotoxin (125I-BoNT) types A and B at the vertebrate neuromuscular junction were investigated using electron microscopic autoradiography. data obtained allow following conclusions to be made. 125I-BoNT type A, applied in vivo or vitro mouse diaphragm frog cutaneous pectoris muscle, interacts saturably with motor nerve terminal only; silver grains occur on plasma membrane, within synaptic bouton, axoplasm of trunk, suggesting...

Dendrotoxin, a small single-chain protein from the venom of Dendroaspis angusticeps, is highly toxic following intracerebroventricular injection into rats. Voltage-clamp analysis CA1 neurons in hippocampal slices, treated with tetrodotoxin, revealed that nanomolar concentrations dendrotoxin reduce selectively transient, voltage-dependent K conductance. Epileptiform activity known to be induced by can attributed such an action. Membrane currents not affected directly toxin include (i)...

An alpha-bungarotoxin-binding protein was purified from chick optic lobe and brain by an improved method. Previous present observations justify its designation as a nicotinic acetylcholine receptor (AcChoR). It contains subunits whose apparent molecular weights are somewhat larger than those of peripheral AcChoRs. The size the AcChoR complex is greater that when estimated sedimentation behavior. Brain can be specifically precipitated monoclonal antibody directed against muscle AcChoR....

The perhydro derivative of histrionicotoxin reversibly blocks the excitatory ionic transduction system in synaptic and sarcolemmal membranes mammalian skeletal muscle cells. efficacy perhydrohistrionicotoxin as an antagonist at post-synaptic membrane is increased by transient presence acetylcholine endplate innervated muscles extrajunctional receptors denervated muscles. alpha-Bungarotoxin [(3)H]monoacetyl-alpha-bungarotoxin block receptors, each binding to same extent. effect bungarotoxin...

Abstract Transient receptor potential (TRP) A1 and V1 channels relay sensory signals, yet little is known about their transport to the plasmalemma during inflammation. Herein, TRPA1 TRPV1 were found on vesicles containing calcitonin gene-related peptide (CGRP), accumulated at sites of exo- endo-cytosis co-localised fibres cell bodies cultured neurons expressing both. A proinflammatory cytokine, TNFα, elevated surface content both resided in close proximity, indicating co-trafficking....

Previous electrophysiological evidence has indicated that astrocytes and oligodendrocytes express inwardly rectifying K+ channels both in vitro vivo. Here, for the first time, we have undertaken light microscopic immunohistochemical studies demonstrating location of one such channel, Kir4.1, cell types regions rat CNS. Some as those deep cerebellar nuclei, Bergmann glia, retinal Müller cells, a subset hippocampus Kir4.1 immunoreactivity, but not others including white matter....

Voltage-dependent cation channels are large heterooligomeric proteins. Heterologous expression of cDNAs encoding the alpha subunits alone K+, Na+, or Ca2+ produces functional multimeric proteins; however, coexpression those for latter two with their auxiliary proteins causes dramatic changes in resultant membrane currents. Fast-activating, voltage-sensitive K+ from brain contain four and beta subunits, tightly associated a 400-kDa complex; although molecular details alpha-subunit have been...

Abstract : The α subunits of Shaker‐related K + channels (Kv1.X) show characteristic distributions in mammalian brain and restricted coassembly. Despite the functional importance these voltage‐sensitive involvement a number diseases, little progress has been achieved deciphering subunit composition (α) 4 (β) oligomers occurring human CNS. Thus, association β was investigated cerebral grey white matter spinal cord from autopsy samples. Immunoblotting established presence Kv1.1, 1.2, 1.4 all...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAntibodies specific for distinct Kv subunits unveil a heterooligomeric basis subtypes of .alpha.-dendrotoxin-sensitive potassium channels in bovine brainVictoria E. S. Scott, Zilda M. Muniz, Sabine Sewing, Ralf Lichtinghagen, David N. Parcej, Olaf Pongs, and J. Oliver DollyCite this: Biochemistry 1994, 33, 7, 1617–1623Publication Date (Print):February 22, 1994Publication History Published online1 May 2002Published inissue 22 February...

Voltage-dependent Shaker-related (Kv1) K+ channels are composed of transmembrane alpha subunits and peripheral Kv beta proteins that exist as octomers with (alpha)4(beta)4 stoichiometry. Although several (designated Kv1.X) three known to be expressed in brain, their oligomeric combinations neurons have yet deciphered. Herein, the comprising a number neuronal from bovine brain cortex were deduced by immunoprecipitation Western blotting, using antibodies specific for Kv1.X subtypes. Only...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOligomeric properties of .alpha.-dendrotoxin-sensitive potassium ion channels purified from bovine brainDavid N. Parcej, Victoria E. S. Scott, and J. Oliver DollyCite this: Biochemistry 1992, 31, 45, 11084–11088Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/bi00160a018https://doi.org/10.1021/bi00160a018research-articleACS PublicationsRequest...