scholarly journals Acetylcholine receptors in the equatorial region of intrafusal muscle fibres modulate mouse muscle spindle sensitivity

2019 ◽  
Vol 597 (7) ◽  
pp. 1993-2006 ◽  
Author(s):  
Laura Gerwin ◽  
Corinna Haupt ◽  
Katherine A. Wilkinson ◽  
Stephan Kröger

1. The sensory nerve contacts in the muscle spindle of the frog were examined in the electron microscope. 2. The terminal branches of the sensory axon form long beaded chains, i.e. bulbous expansions up to 2 to 3 ix thick connected in series by thin cylinders of as little as 0.15 ju. diameter. Many nerve bulbs are seated in cup-like depressions of the intrafusal muscle fibres forming close contact with them. There is a residual gap between nerve and muscle surfaces of about 150 Å, but the gap is bridged here and there by fine filaments or processes of one cell closely approaching or touching the other. 3. The region of sensory contacts along the intrafusal fibres extends over several hundred microns and is divided into two morphologically distinct types of zones: ( a ) two ‘compact’ zones at either end, each about 300 /u. long, in which the fibre retains approximately the same size and number of myofilaments as in the remote, extracapsular, region; ( b ) a ‘reticular’ zone in the centre, about 100 /rlong, in which the fibre loses some 85 % of its content of filaments and splays out into several fins and branches held together by slender membrane connexions. The interstices between the splayed-out parts are filled with a dense network of fine connective tissue fibrils (about 50 Å thick). A minority of the intrafusal fibres does not show this differentiation in the sensory region and retains most of its myofilaments throughout. 4. Several characteristic differences are described between motor and sensory nerve endings on intrafusal muscle fibres. Among them are ( a ) that the motor terminal forms an ‘epectolemmal’, the sensory ending a ‘ hypectolemmaP contact (referring to the external basement membrane of the cells as the ‘ectolemma’) ; ( b ) the motor ending remains invested by a covering Schwann cell layer, while the sensory endings are not closely associated with satellite cells; ( c ) the cytoplasm of motor endings is characterized by an accumulation of 500 Å vesicles near the synaptic surface, that of sensory endings by an accumulation of small mitochondria. 5. A structure of unusual periodicity (a longitudinal ‘micro-ladder with rungs about 1600 Å apart) was observed in the interior of intrafusal muscle fibres, located generally in the neighbourhood of sensory nerve contacts. 6. The functional significance of some of the observed morphological features is discussed. It is suggested that mechanical stimulation and depolarization of the sensory nerve endings occurs at the points of adhesion between the intrafusal muscle fibre and the terminal nerve bulbs. The differentiation between ‘dynamic’ and ‘static’ components of the sensory stretch response may arise from different visco-elastic properties of the ‘compact’ and ‘reticular’ zones. Motor activation of the intrafusal muscle fibres would lead to intense stimulation of the sensory endings mainly within the ‘reticular’ zone. This zone is protected against overstretching by a feltwork of connective tissue fibrils.


2004 ◽  
Vol 123 (4) ◽  
pp. 341-356 ◽  
Author(s):  
Sudha Chakrapani ◽  
Timothy D. Bailey ◽  
Anthony Auerbach

We used single-channel recording and model-based kinetic analyses to quantify the effects of mutations in the extracellular domain (ECD) of the α-subunit of mouse muscle–type acetylcholine receptors (AChRs). The crystal structure of an acetylcholine binding protein (AChBP) suggests that the ECD is comprised of a β-sandwich core that is surrounded by loops. Here we focus on loops 2 and 7, which lie at the interface of the AChR extracellular and transmembrane domains. Side chain substitutions in these loops primarily affect channel gating by either decreasing or increasing the gating equilibrium constant. Many of the mutations to the β-core prevent the expression of functional AChRs, but of the mutants that did express almost all had wild-type behavior. Rate-equilibrium free energy relationship analyses reveal the presence of two contiguous, distinct synchronously-gating domains in the α-subunit ECD that move sequentially during the AChR gating reaction. The transmitter-binding site/loop 5 domain moves first (Φ = 0.93) and is followed by the loop 2/loop 7 domain (Φ = 0.80). These movements precede that of the extracellular linker (Φ = 0.69). We hypothesize that AChR gating occurs as the stepwise movements of such domains that link the low-to-high affinity conformational change in the TBS with the low-to-high conductance conformational change in the pore.


2003 ◽  
Vol 550 (1) ◽  
pp. 263-278 ◽  
Author(s):  
R. Durbaba ◽  
A. Taylor ◽  
P. H. Ellaway ◽  
S. Rawlinson

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