5-hydroxytryptamine blocks the fetal more potently than the adult mouse muscle acetylcholine receptor.
The action of 5-hydroxytryptamine (5-HT) on fetal (gamma-AChR) and adult (epsilon-AChR) muscle acetylcholine receptors was studied in transfected BOSC 23 cells expressing mouse AChRs and in acutely dissociated mouse muscle fibres. In transfected cells, coapplication of 5-HT (0.01-10 mM) with ACh reversibly reduced the amplitude and accelerated the decay of the ACh-activated whole-cell currents, in a dose- and voltage-dependent manner. 5-HT blocked faster and with higher potency the gamma-AChR than the epsilon-AChR. Cell-attached recordings from transfected BOSC 23 cells and embryonic or neonatal muscle fibres were made. When 5-HT (5 microM) was included in the patch pipette, ACh-evoked unitary events acquired a bursting behaviour, which was more pronounced for gamma- than epsilon-AChR, though it was enhanced by membrane hyperpolarization for both AChR species. There was no effect on the single-channel conductance. It is concluded that 5-HT behaves as an open-channel blocker of muscle AChRs, with higher efficacy on gamma- than on epsilon-AChR.
Grassi
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Istituto Pasteur-Fondazione Cenci Bolognetti and Dipartimento di Medicina Sperimentale, Universita "La Sapienza" V. le Regina Elena 324, I-00161 Rome, Italy.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004553:Electric Conductivity; D015870:Gene Expression; D006801:Humans; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000737:chemistry / Q000196:embryology* / Q000254:growth & development*; D009469:Neuromuscular Junction / Q000737:chemistry / Q000196:embryology / Q000254:growth & development; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D014162:Transfection
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D012701:Serotonin; D000109:Acetylcholine