Neuregulin effect on quantal content dissociated from effect on miniature endplate potential amplitude.
Members of the neuregulin family of signaling proteins increase transcription of acetylcholine receptor (AChR) subunit genes in muscle fibers and the number of AChRs in the muscle membrane. In adult mice heterozygous for targeted deletion of type I neuregulins (Ig-NRG(+/-)), postsynaptic AChR density was decreased and transmitter release was increased. We examined the relationship between functional AChR density and ACh release in postnatal day 7 (P7), P14, and adult NRG-deficient mice. Here we report that changes in postsynaptic sensitivity and transmitter release are not temporally coupled during postnatal development in Ig-NRG-deficient mice. Although miniature endplate potential (MEPP) amplitude was decreased compared with control in P7 Ig-NRG(+/-) mice, quantum content was not increased. Quantum content was increased in adult heterozygotes despite normal MEPP amplitudes. Thus, during postnatal maturation, both quantal size and quantum content were influenced by decreased Ig-NRG expression, although the effects were dissociated in time.
Mann
Mary Anne
MA
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. mam2012@columbia.edu
Das
Saumya
S
Zhang
Jinghua
J
Wagner
Meredith
M
Fischbach
Gerald D
GD
D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D004558:Electric Stimulation; D004622:Embryo, Mammalian / Q000502:physiology; D019054:Evoked Potentials, Motor / Q000187:drug effects*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009045:Motor Endplate / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D020880:Neuregulins / Q000235:genetics / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D009435:Synaptic Transmission / Q000187:drug effects
D002038:Bungarotoxins; D020880:Neuregulins; D018377:Neurotransmitter Agents; D012333:RNA, Messenger