In the presence of carnosine, anserine, histidine, imidazole and 7-nitro indazole, the early postdenervation depolarization of muscle of about 8 mV was significantly increased by 2.15-4.8 mV. The presence of the imidazole ring in the molecule is apparently necessary for this effect. These compounds also eliminated an NO-mediated protective effect of L-glutamate and carbachol on the depolarization of membrane potential. The presence of imidazole, 7-nitro indazole, carnosine and anserine did not significantly change the effect of an external NO donor, sodium nitroprusside. The structural and fuhctional similarity between imidazole derivatives and the known NO synthase inhibitor, 7-nitro indazole suggests that imidazole, carnosine and anserine might act by inhibiting NO production which is stimulated by glutamate and carbachol.
At frog neuromuscular junction, noradrenaline (NA) shortens the release period for evoked quantal release acting on a b 1 receptor. To test the hypothesis that this action of NA is mediated by cAMP, we measured the latencies of focally recorded uni-quantal endplate currents (EPCs) after application of dibutyryl-cAMP (db-cAMP) and adenylyl cyclase activator, forskolin. The interval between the time when responses with minimal delay appeared and the point at which 90 % of all latencies had occurred (P90 parameter) was shortened in the presence of both 1x10-6 mol/l db-cAMP and 1x10-6 mol/l forskolin by about 30 %. The cAMP-induced shortening is equal to that found after application of NA and effects of both drugs are not additive., E. Bukcharaeva, D. Samigullin, E. E. Nikolsky, F. Vyskočil., and Obsahuje bibliografii
Derivative of 6-methyluracil, selective cholinesterase inhibitor C-547 potentiates miniature endplate currents (MEPCs) in rat external intercostal muscles (external ICM) more effectively than in internal intercostal muscles (internal ICM). Effect of the C-547 on intercostal muscles was compared with those on extensor digitorum longus (EDL) and diaphragm muscles. Half-effective concentrations for τ of MEPC decay arranged in increasing order were as follows: EDL, locomotor muscle, most sensitive = 1.3 nM, external ICM, inspiration muscle = 6.8 nM, diaphragm, main inspiration muscle = 28 nM, internal ICM, expiration muscle = 71 nM. External ICM might therefore be inhibited, similarly as the limb muscles, by nanomolar concentrations of the drug and do not participate in inspiration in the presence of the C-547. Moreover, internal ICM inhibition can hinder the expiration during exercise-induced fast breathing of C-547-treated experimental animals., K. Petrov ... [et al.]., and Obsahuje seznam literatury
M1-muscarinic acetylcholine (ACh) receptors (M1R) were directly demonstrated immunocytochemic ally in electronmicroscopic images of rat diaphragm neuromus cular junctions (NMJ). Specific electron-dense granules were located at presynaptic nerve ending membranes and in the sa rcolemma in the depths of postsynaptic folds. This first visualization of M1R on both sides of the NMJ is in agreement with previous pharmacological data on the regulatory role of M1R in quantal and non-quantal ACh release. and Obsahuje bibliografii a bibliografické odkazy
The early postdenervation depolarization of rat diaphragm muscle fibres (8-10 mV) is substantially smaller (3 mV) when muscle strips are bathed with 1 mM L-glutamate (GLÜ) or N-methyl-D-aspartate (NMDA). The effects of GLÜ and NMDA are not seen in the presence of aminophosphonovaleric acid (APV), a blocker of NMDA-subtype of glutamate receptors, 5 mM Mg2+ (which blocks NMDA-controlled ion channels) and L-nitroarginine methylester (NAME), an inhibitor of NO-synthase. This indicates that NMDA-subtype of GL(J receptors might be involved in the regulation of the membrane potential in muscle fibres, most probably through the NO-synthase system.
After anticholinesterase treatment in vivo, depolarization of the postsynaptic muscle fibre membrane by about 4 mV develops due to non-quantally released acetylcholine from the motor nerve terminal. This conclusion was supported by experiments with the curarization of diaphragm slices from anticholinesterase treated mice during intracellular microelectrode recordings.
There are two principal mechanisms of acetylcholine (ACh) release from the resting motor nerve terminal: quantal and non-quantal (NQR); the former being only a small fraction of the total, at least at rest. In the present article we summarize basic research about the NQR that is undoubtedly an important trophic factor during endplate development and in adult neuromuscular contacts. NQR helps to eliminate the polyneural innervation of developing muscle fibers, ensures higher excitability of the adult subsynaptic membrane by surplus polarization and protects the RMP from depolarization by regulating the NO cascade and chloride transport. It shortens the endplate potentials by promoting postsynaptic receptor desensitization when AChE is inhibited during anti-AChE poisoning. In adult synapses, it can also activate the electrogenic Na+/K+-pump, change the degree of synchronization of quanta released by the nerve stimulation and affects the contractility of skeletal muscles., F. Vyskočil, A. I. Malomouzh, E. E. Nikolsky., and Obsahuje seznam literatury
The effect of Na+-K+-ATPase inhibitor ouabain on the resting membrane potential (Vm) was studied by glass microelectrodes in isolated somatic longitudinal muscles of the earthworm Lumbricus terrestris and compared with frog sartorius muscle. In earthworm muscle, Vm was -49 mV (inside negative) in a reference external solution with 4 mmol/l K+. The electrogenic participation of Na+-K+-ATPase was absent in solutions with very low concentrations of 0.01 mmol/l K+, higher in 4 and 8 mmol/l K+ (4-5 mV) and maximal (13 mV) in solutions containing 12 mmol/l K+ where Vm was -46 mV in the absence and -33 mV in the presence of 1x10-4 M ouabain. The electrogenic participation of Na+-K+-ATPase was much smaller in m. sartorius of the frog Rana temporaria bathed in 8 and 12 mmol/l K+. The results indicate that the Na+-K+-ATPase is an important electrogenic factor in earthworm longitudinal muscle fibres and that its contribution to Vm depends directly on the concentration of K+ in the bathing solution., E. M. Volkov, L. F. Nurullin, I. Švandová, E. E. Nikolsky, F. Vyskočil., and Obsahuje bibliografii
It is well known that antagonists of N-type voltage-gated calcium channels inhibit the evoked quan tal release of acetylcholine in amphibian neuromuscular synapses. This, however, does not exclude the functional expression of other types of voltage-gated calcium channels in these nerve terminals. Using immunocytochemistry, we detected the expression of the α1A subunit of P/Q-type calcium channels (that is otherwise typical of mammalian motor nerve endings) in the frog neuromuscular junction. In addition, we demonstrated that the P/Q-type channel blocker ω-agatoxin IVA (20 nM) reduced the action potential- induced calcium transient and significantly decreased both spontaneous and evoked mediator release. Our data indicates the functional expression of P/Q-type calcium channels in the frog motor nerve ending which participate in acetylcholine release., L. F. Nurullin ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy