Disease relevance of Apamin

• Binding and toxicity of apamin. Characterization of the active site [1].
• Local apamin poisoning differs from local tetanus (elicited by the same way) by its faster time course [2].
• Apamin, a bee venom polypeptide, is reported to block the Ca2+-dependent K+ channel in smooth muscle, hepatocyte, and neuroblastoma cells [3].
• Expression of apamin receptor in muscles of patients with myotonic muscular dystrophy [4].
• Possible role of apamin-sensitive K+ channels in myotonic dystrophy [5].

High impact information on Apamin

• Single apamin-blocked Ca-activated K+ channels of small conductance in cultured rat skeletal muscle [6].
• We show here for the first time that muscle membranes of patients with myotonic muscular dystrophy contain the receptor for apamin, a bee venom toxin known to be a specific and high-affinity blocker of one class of Ca2+-activated K+ channels in mammalian muscle [4].
• Apamin is a neurotoxic polypeptide of known structure isolated from bee venom [7].
• The Ca2+-dependent slow K+ conductance in cultured rat muscle cells: characterization with apamin [8].
• Voltage-clamp analyses have shown that apamin, at low concentrations, specifically blocks the Ca2+-dependent slow K+ conductance in rat myotubes and myosacs . A specific binding site for apamin in rat muscle cell membranes has been characterized with the use of a highly radiolabelled apamin derivative [( 125I]apamin) [8].

Chemical compound and disease context of Apamin

• In 2 controls and in 2 patients with generalized myotonia, as well as in 1 patient with myotonia congenita (where the defect is in chloride channels), apamin had no effect [5].

Biological context of Apamin

• From a cDNA library prepared from venom glands of worker bees, clones encoding the precursors of apamin and MCD peptide have been isolated [9].
• The sequence of this segment shows 81% identity to the DNA sequence preceding the first exon of the apamin gene and both contain a putative TATA box [9].
• Starting from the 5'-end, these exons are arranged in the following order: three exons of the mast cell-degranulating (MCD) peptide precursor, two exons of the gene for the apamin precursor, and finally a 3'-exon present in both cDNAs [9].
• The structural features of apamin, a natural octadecapeptide from bee venom, enabling binding to its receptor and the expression of toxicity in mice, have been delineated by studying the effects on binding and toxicity of chemical modifications and amino acid substitutions in synthetic analogues [1].
• Apamin (10-100 nM) inhibited K(+) current activation and cell volume recovery from swelling [10].

Anatomical context of Apamin

• Ion pair reagents were required to resolve the strongly basic peptides, secapin, mast cell degranulating (MCD-) peptide and apamin, by reversed-phase (RP) HPLC [11].
• Apamin converted the hyperpolarization caused by ATP or Adr into a transient depolarization which produced contraction of the muscle cells [12].
• In contrast, saturable binding of 125I-apamin to rat liver plasma membranes was virtually undetectable, thereby providing a correlation with the ability to measure apamin-sensitive Ca(2+)-activated potassium currents in rabbit and guinea pig hepatocytes but not in rat hepatocytes [13].
• Affinity labeling was abolished on both liver and brain membranes by apamin, scyllatoxin, dequalinium, gallamine, and d-tubocurarine [13].
• (iv) Apamin receptors detected with 125I-labeled apamin are present at fetal stages with biochemical characteristics identical to those found in myotubes in culture [14].

Associations of Apamin with chemical compounds

• Thus, apamin folding is very cooperative, but the native structure is only modestly stabilized by urea- or temperature-denaturable secondary structure [15].
• In contrast to apamin, it is hardly neurotoxic upon intravenous injection in mice [2].
• An Amino Acid Outside the Pore Region Influences Apamin Sensitivity in Small Conductance Ca2+-activated K+ Channels [16].
• 5. Apamin (10 nM) also abolished the increase in 42K efflux which follows the application of the alpha-adrenoceptor agonist amidephrine to rabbit liver slices; the concurrent rises in 45Ca efflux and glucose release were unaffected [17].
• Apamin, in contrast to quinine or A23187, also failed to affect bioelectrical activity in mouse islet cells [18].

Other interactions of Apamin

• It is further suggested that apamin, mast cell degranulating peptide and tertiapin form a single molecular class [19].
• The four major protein peaks eluted were identified as hyaluronidase, phospholipase, melittin, and apamin [20].
• All patients were insensitive to the hyaluronidase and apamin preparations [20].
• 1. The m. triangularis sterni of the mouse was used to investigate the actions of dendrotoxin, beta-bungarotoxin, crotoxin, taipoxin, bee venom phospholipase A2, aprotinin and apamin on presynaptic currents which flow inside the perineural sheath of nerve bundles upon nerve stimulation [21].

Analytical, diagnostic and therapeutic context of Apamin

• (ii) Extensor digitorum longus muscles from adult rats have action potentials that are not followed by AHP but AHP are systematically recorded after muscle denervation and they are blocked by apamin [14].
• An apamin-like factor has been isolated from pig brain after extraction of the tissue and purification on sulfopropyl-Sephadex C-25 and on reversed-phase high pressure liquid chromatography [22].
• Crystallization and preliminary X-ray diffraction data of the Fab fragment of a monoclonal antibody against apamin, a bee venom neurotoxin [23].
• The synthetic peptide showed the same physiochemical and chemical properties as natural apamin in the following tests: paper electrophoresis, amino acid analyses after acid and enzymatic hydrolyses, sequence analysis, electrophoreses after tryptic and chymotryptic digestions [24].
• Using microelectrodes to record intracellularly from rat dopamine neurons in the midbrain slice, BMI reduced the apamin-sensitive afterhyperpolarization in all cells tested [25].

References