Involvement of Na,K-pump in SEPYLRFamide-mediated reduction of cholinosensitivity in Helix neurons.
SEPYLRFamide acts as an inhibitory modulator of acetylcholine (ACh) receptors in Helix lucorum neurones. Ouabain, a specific inhibitor of Na,K-pump, (0.1 mM, bath application) decreased the ACh-induced inward current (ACh-current) and increased the leak current. Ouabain decreased the modulatory SEPYLRFamide effect on the ACh-current. There was a correlation between the effects of ouabain on the amplitude of the ACh-current and on the modulatory peptide effect. Ouabain and SEPYLRFamide inhibited the activity of Helix aspersa brain Na,K-ATPase. Activation of Na,K-pump by intracellular injection of 3 M Na acetate or 3 M NaCl reduced the modulatory peptide effect on the ACh-current. An inhibitor of Na/Ca-exchange, benzamil (25 muM, bath application), and an inhibitor of Ca(2+)-pump in the endoplasmic reticulum, thapsigargin (TG, applied intracellularly), both prevented the effect of ouabain on SEPYLRFamide-mediated modulatory effect. Another inhibitor of Ca(2+)-pump in the endoplasmic reticulum, cyclopiazonic acid (applied intracellularly), did not prevent the effect of ouabain on SEPYLRFamide-mediated modulatory effect. These results indicate that Na,K-pump is responsible for the SEPYLRFamide-mediated inhibition of ACh receptors in Helix neurons. Na/Ca-exchange and intracellular Ca(2+) released from internal pools containing TG-sensitive Ca(2+)-pump are involved in the Na,K-pump pathway for the SEPYLRFamide-mediated inhibition of ACh receptors.
Pivovarov
Arkady S
AS
Department of Higher Nervous Activity, Biological Faculty, Moscow Lomonosov State University, Leninskie Gory, dom 1, korpus 12, Moscow 119992, Russia.
Foreman
Richard C
RC
Walker
Robert J
RJ
D000085:Acetates / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006372:Helix, Snails / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D000085:Acetates; D004791:Enzyme Inhibitors; D007211:Indoles; D009479:Neuropeptides; C118200:SEPYLRFamide; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D012965:Sodium Chloride; D010042:Ouabain; D019284:Thapsigargin; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D002118:Calcium; C000543:cyclopiazonic acid