Adaptation of quantal content to decreased postsynaptic sensitivity at single endplates in alpha‐bungarotoxin‐treated rats.

Abstract

SUMMARY1. Rats were injected once every 48 h with a-bungarotoxin (aBTX) for periods up to 6 weeks. Injections caused weakness of facial muscles which lasted about 8 h. Hemidiaphragms were dissected for biochemical and electrophysiological measurements.2. In muscles from animals treated for 2-3 weeks with toxin, the binding of 125-aBTX was reduced to 58 %, and the ACh content to 81 % of control values. Choline acetyltransferase activity was unchanged. ACh release evoked by 3 Hz nerve stimulation was increased to 175 % of control values.3. The use of ,u-conotoxin, which specifically blocks muscle action potentials, enabled the recording of full-sized endplate potentials (EPPs) and miniature endplate potentials (MEPPs) at normal muscle membrane potentials ( -70 to -80 mV). The amplitude of MEPPs was decreased to 57 % in muscles from animals treated for 3 weeks with aBTX. The mean of the quantal contents, calculated from the ratio of the corrected EPPs and the MEPPs, was increased to 154 %.4. Within individual muscles of both acBTX-treated and control rats, there was an inverse relationship between the quantal content of an endplate and its MEPP amplitude.5. The MEPP frequency of endplates from control muscles was positively correlated with the quantal content. However, this correlation was not found in aBTX-affected muscles.6. Three hours after a single injection of aBTX the amplitude of the MEPPs was reduced to about 60 % of control values but no increase of the quantal content was found. During the first few days of aBTX treatment the quantal content gradually increased; it reached a plateau between 20 and 30 days.7. The results suggest the existence of an adaptive mechanism, operating at individual endplates, in which retrograde signals at the motor nerve terminals modulate ACh release when neuromuscular transmission is endangered by block of acetylcholine receptors. MS 1036 J. J. PLOMP AND OTHERS

Regulation of Motoneuron Excitability via Motor Endplate Acetylcholine Receptor Activation

“…The increase of motoneuron excitability observed in this study (Fig. 2) and the increase of ACh release observed by others after AChR blockade (Plomp et al, 1992(Plomp et al, , 1994) may both be initiated by lost retrograde signaling and represent an integrated attempt by the motoneuron to maintain motor unit force output in the face of decreased AChR density at the endplate. Although retrograde signaling from muscle may be vital for determining motoneuron functional properties, it is also important to keep in mind the pivotal role of anterograde signaling from motoneurons for establishing mechanisms that likely enable retrograde signaling via AChR activation.…”

“…In eight fibers, the amplitude of the fourth EPC in a 50 Hz train was 37.6 Ϯ 4.4% (n ϭ 8) of the first EPC amplitude, whereas the same comparison yielded 80.3 Ϯ 1.5% in four control experiments, each of which included sampling from at least seven fibers. Previous studies have shown that the amount of ACh released at motor terminals increases significantly after several weeks of partial AChR blockade with ␣-btx, and this is thought to be a compensatory response to decreased AChR density (Plomp et al, 1992(Plomp et al, , 1994. The increased EPC amplitude depression during low-and high-frequency activation might thus reflect an increased quantal content at motor terminals.…”

The RhoGAPcrossveinless-cInteracts withDystrophinand Is Required for Synaptic Homeostasis at theDrosophilaNeuromuscular Junction

“…This led us to speculate that retrograde signaling from the muscle to motoneuron is altered in the Dys mutant. Retrograde signaling pathways influencing neurotransmitter release have also been inferred in previous murine and Drosophila studies (Plomp et al, 1992;Davis and Bezprozvanny, 2001;Turrigiano and Nelson, 2004), including those focused on the Drosophila larval NMJ (Marqués and Zhang, 2006). Little is known, however, about the components of these pathways.…”

Increased Neurotransmitter Release at the Neuromuscular Junction in a Mouse Model of Polyglutamine Disease

“…To minimize errors in the quantal content estimation, we have corrected the effect of nonlinear summation on EPP amplitude as previously described (McLachlan and Martin, 1981) using a correction factor ( f ϭ 0.8) (see Materials and Methods). The introduction of that factor improves overcorrection introduced by older methods (Martin, 1955), and it has been used in different mouse neuromuscular preparations (Plomp et al, 1992;Wood and Slater, 1997;Bullens et al, 2002;Bewick et al, 2004;Chen et al, 2010). Current-clamp measurements of quantal content could be relatively inaccurate if compared with absolute quantal content values obtained with voltage-clamp recordings as previously described in other preparations (Wood and Slater, 1997).…”