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.

Effect of oxygen at high pressure on spontaneous transmitter release

The effect of oxygen at high pressure (OHP) on resting membrane properties (effective membrane resistance (Reff) and membrane potential (Vm)) and the spontaneous release of excitatory transmitter were examined at the lobster neuromuscular junction. Pressurization with 100% oxygen to 150 pounds per square inch gauge pressure (psig) or with nitrogen to 150 psig (7,000 mmHg nitrogen and 135 mmHg oxygen) produced a decrease in Reff associated with a hyperpolarization of Vm. These changes, however, returned to control values within 20--30 min after completion of pressurization. Spontaneous release of excitatory transmitter was shown to increase dramatically in the presence of 100% oxygen at 150 psig. The increase in miniature end-plate potential (MEPP) frequency persisted beyond the transient changes seen with Reff and Vm. This effect was selective to oxygen, as pressurization with nitrogen did not produce an increase in MEPP frequency. No change in average MEPP amplitude was seen with either OHP or pressure alone. An OHP-induced increase in MEPP frequency was also seen at the frog neuromuscular junction. The results indicate that both glutamate-mediated and acetylcholine-mediated synaptic transmission are altered by OHP.

Multimodal Distribution of Frog Miniature Endplate Potentials in Adult, Denervated, and Tadpole Leg Muscle

Amplitude histograms of spontaneous miniature endplate potentials (MEPPs) from adult sartorius muscle cells show a definite bimodality with the mean amplitude of the larger mode five to seven times that of the smaller mode which accounted for 2–5 % of the total MEPPs. Histograms were plotted after high frequency MEPP generation induced by increasing temperature, increasing external calcium or nerve stimulation. These plots showed a reversible left-shift of the major mode as well as a reversible increase in the proportion of small mode MEPPs. Repeated challenges shifted almost all MEPPs into the small mode. An increase in the percentage of small mode MEPPs also occurred spontaneously during the course of denervation before the quiescent period and some of the histogram profiles showed multiple modes whose means were integer multiples of the small mode mean. In the early stages of hind leg development the greatest proportion of MEPPs were of the small mode size; as metamorphosis progressed, the histograms showed a definite multimodality with the mean of each mode being an integer multiple of the small mode mean and with the proportion of MEPPs in each mode about the same. During tail resorption the percentage of larger MEPPs increased until the adult histogram profile was reached. Thus, the changes in MEPP amplitude histograms over the course of metamorphosis are the reverse of those found with denervation.