One element, potassium, can be identified as the connecting link in the research of Czech neurophysiologist Prof. František Vyskočil. It accompanied him from the first student experiments on the frog muscle (Solandt effect) via sodium-potassium pump and quantum and non-quantum release of neurotransmitters (e.g. acetylcholine) to the most appreciated work on the reversible leakage of K+ from brain neurons during the Leao´s spreading cortical depression, often preceding migraine. He used a wide range of methods at the systemic, cellular and genetic levels. The electrophysiology and biochemistry of nerve-muscle contacts and synapses in the muscles and brain led to a range of interesting findings and discoveries on normal, denervated and hibernating laboratory mammals and in tissue cultures. Among others, he co-discovered the facilitating effects of catecholamines (adrenaline in particular) by end-plate synchronization of individual evoked quanta. This helps to understand the general effectiveness of nerve-muscle performance during actual stress. After the transition of the Czech Republic to capitalism, together with Dr. Josef Zicha from our Institute, he was an avid promoter of scientometry as an objective system of estimating a scientist´s success in basic research (journal Vesmír, 69: 644-645, 1990 in Czech).

• MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Brain * physiology   metabolism   MeSH
• Neurons * metabolism   physiology   MeSH
• Neurosciences * MeSH
• Anura MeSH
• Animals MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Review MeSH

Resting non-quantal acetylcholine (ACh) and probably glutamate (Glu) release from nerve endings activates M1- and NMDA receptor-mediated Ca2+ entry into the sarcoplasm with following activation of NOS and production of NO. This is a trophic message from motoneurons, which keeps the Cl- transport inactive in the innervated sarcolemma. After denervation, the secretion of ACh and Glu at the neuromuscular junction is eliminated within 3-4 h and the production of NO in the sarcoplasm is lowered. As a result, the Cl- influx is probably activated by dephosphorylation of the Cl- transporter with subsequent elevation of intracellular Cl- concentration. The equilibrium Cl- potential becomes more positive and the muscle membrane becomes depolarized.

• MeSH
• Acetylcholine physiology   MeSH
• Chlorides metabolism   MeSH
• Muscle Denervation * MeSH
• Electrophysiology MeSH
• Muscle, Skeletal physiology   MeSH
• Glutamic Acid physiology   MeSH
• Nitric Oxide metabolism   MeSH
• Carrier Proteins physiology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Acetylcholine MeSH
• Chlorides MeSH
• Glutamic Acid MeSH
• Nitric Oxide MeSH
• Carrier Proteins MeSH

1. Rat hemidiaphragms were incubated in a physiological low-K+ medium without stimulation and the amount of acetylcholine (ACh) released was measured radioenzymatically. Cholinesterases were inhibited by paraoxon. 2. In the presence of 1 microM tetrodotoxin (TTX), the amount of ACh released during a 2 h incubation was lowered by 40%. A similar decrease was observed in the absence of Ca2+ and in the presence of 10 microM-d-tubocurarine (dTC). The effects of TTX combined with Ca2+ removal, and of TTX combined with dTC were no greater than those of TTX, dTC or Ca2+ removal alone. TTX and dTC had no effect on the release of ACh from diaphragms 4 days after denervation. 3. The reduction of spontaneous ACh release observed in the presence of TTX or dTC or in the absence of Ca2+ is best interpreted on the assumption that about 40% of the ACh release was due to the impulse activity known to be generated in intramuscular motor nerve branches by the ACh which accumulates after the inhibition of cholinesterases. 4. In the presence of 1 and 10 microM vesamicol (AH5183, 2-(4-phenylpiperidino)-cyclohexanol), the release of ACh was also diminished by approximately 40%. Vesamicol did not augment the inhibition of release produced by TTX or by the omission of Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

• MeSH
• Acetylcholine metabolism   MeSH
• Diaphragm MeSH
• Time Factors MeSH
• Depression, Chemical MeSH
• Cholinesterases physiology   MeSH
• Denervation MeSH
• Neuromuscular Depolarizing Agents pharmacology   MeSH
• Rats MeSH
• Piperidines pharmacology   MeSH
• Rats, Wistar MeSH
• Muscles innervation   metabolism   MeSH
• In Vitro Techniques MeSH
• Tetrodotoxin pharmacology   MeSH
• Tubocurarine pharmacology   MeSH
• Calcium physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Acetylcholine MeSH
• Cholinesterases MeSH
• Neuromuscular Depolarizing Agents MeSH
• Piperidines MeSH
• Tetrodotoxin MeSH
• Tubocurarine MeSH
• Calcium MeSH
• vesamicol MeSH Browser

1. Acetylcholine (ACh), 7.5 x 10(-5) M, and carbachol, 5 x 10(-6) M (CCh) depressed the frequency of miniature endplate potentials (m.e.p.ps) in the frog (Rana temporaria) sartorius neuromuscular junction with active acetylcholinesterase to about 50-55% of the controls. 2. A similar depression was produced by the nicotinic agonists, nicotine, suberyldicholine and tetramethylammonium. 3. The muscarinic agonists, oxotremorine, methylfurmethide and methacholine were without effect on m.e.p.p. frequency. The muscarinic antagonist, atropine and the nicotinic antagonist, (+)-tubocurarine, had no effect on the depression of m.e.p.p. frequency evoked by CCh. 4. The ganglionic blockers, benzhexonium and IEM-1119, were also without effect on the CCh-evoked depression of m.e.p.p. frequency. 5. Pretreatment of muscles with anticholinesterases did not prevent the CCh-induced drop in m.e.p.p. frequency. 6. The effect of CCh was proportionally the same as in the controls in preparations where the m.e.p.p. frequency was changed by elevation of K+ and in the presence of theophylline, noradrenaline, dibutyryl adenosine 3':5'-cyclic monophosphate (db cyclic AMP) and db cyclic GMP. 7. An inhibitor of Na+,K(+)-ATPase, ouabain, 5 x 10(-5) mol l-1, prevented or reversed the depression of m.e.p.p. frequency by CCh. However, the depression was present in a nominally K(+)-free medium. Insulin and adrenaline, which are considered to be Na+,K(+)-ATPase activators, were without effect on depression of m.e.p.p. frequency. 8. The depression of m.e.p.p. frequency by 5 x 10(-6) M CCh was the same at temperatures between 5 and 30 degrees C with a Q10 near to 1.0. When threshold amounts of CCh were used (6 x 10-7 and 3 x 10-7 M), the depression was less at higher temperatures.9. The receptive structures responsible for the CCh (or ACh)-evoked depression of m.e.p.p. frequency differ pharmacologically from muscarinic, nicotinic ganglionic and neuromuscular junction ACh-receptors as well as from the synaptic cholinesterase, in contrast to previous reports (Duncan & Publicover, 1979).The low temperature-dependence points to the possibility that physical rather than biochemical processes are limiting in this presynaptic effect of cholinomimetics.

• MeSH
• Acetylcholine analogs & derivatives   pharmacology   MeSH
• Enzyme Activation drug effects   MeSH
• Depression, Chemical MeSH
• Chlorides metabolism   MeSH
• Bucladesine pharmacology   MeSH
• Dibutyryl Cyclic GMP pharmacology   MeSH
• Potassium metabolism   MeSH
• Carbachol pharmacology   MeSH
• Membrane Potentials drug effects   MeSH
• Motor Endplate drug effects   MeSH
• Neuromuscular Junction drug effects   MeSH
• Parasympatholytics pharmacology   MeSH
• Parasympathomimetics pharmacology   MeSH
• Rana temporaria MeSH
• Sodium metabolism   MeSH
• Sodium-Potassium-Exchanging ATPase metabolism   MeSH
• In Vitro Techniques MeSH
• Temperature MeSH
• Theophylline pharmacology   MeSH
• Calcium metabolism   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Acetylcholine MeSH
• Chlorides MeSH
• Bucladesine MeSH
• Dibutyryl Cyclic GMP MeSH
• Potassium MeSH
• Carbachol MeSH
• Parasympatholytics MeSH
• Parasympathomimetics MeSH
• Sodium MeSH
• Sodium-Potassium-Exchanging ATPase MeSH
• Theophylline MeSH
• Calcium MeSH