An allometric analysis of the number of muscle spindles in relation to muscle mass in mammalian (mouse, rat, guinea‐pig, cat, human) skeletal muscles is presented. It is shown that the trend to increasing number as muscle mass increases follows an isometric (length) relationship between species, whereas within a species, at least for the only essentially complete sample (human), the number of spindles scales, on average, with the square root rather than the cube root of muscle mass. An attempt is made to reconcile these apparently discrepant relationships. Use of the widely accepted spindle density (number of spindles g⁻¹ of muscle) as a measure of relative abundance of spindles in different muscles is shown to be grossly misleading. It is replaced with the residuals of the linear regression of ln spindle number against ln muscle mass. Significant differences in relative spindle abundance as measured by residuals were found between regional groups of muscles: the greatest abundance is in axial muscles, including those concerned with head position, whereas the least is in muscles of the shoulder girdle. No differences were found between large and small muscles operating in parallel, or between antigravity and non‐antigravity muscles. For proximal vs. distal muscles, spindles were significantly less abundant in the hand than the arm, but there was no difference between the foot and the leg.

Acid-sensing ion channel 3 (ASIC3) is involved in acid nociception, but its possible role in neurosensory mechanotransduction is disputed. We report here the generation ofAsic3-knockout/eGFPf-knockinmice and subsequent characterization of heterogeneous expression of ASIC3 in the dorsal root ganglion (DRG). ASIC3 is expressed in parvalbumin (Pv+) proprioceptor axons innervating muscle spindles. We further generate a floxed allele ofAsic3(Asic3^f/f) and probe the role of ASIC3 in mechanotransduction in neurite-bearing Pv+ DRG neurons through localized elastic matrix movements and electrophysiology. Targeted knockout ofAsic3disrupts spindle afferent sensitivity to dynamic stimuli and impairs mechanotransduction in Pv+ DRG neurons because of substrate deformation-induced neurite stretching, but not to direct neurite indentation. In behavioural tasks, global knockout (Asic3^−/−) andPv-Cre::Asic3^f/fmice produce similar deficits in grid and balance beam walking tasks. We conclude that, at least in mouse, ASIC3 is a molecular determinant contributing to dynamic mechanosensitivity in proprioceptors.

The focus of this review is on the principal sensory ending of the mammalian muscle spindle, known as the primary ending. The process of mechanosensory transduction in the primary ending is examined under five headings: (i) action potential responses to defined mechanical stimuli—representing the ending's input–output properties; (ii) the receptor potential—including the currents giving rise to it; (iii) sensory-terminal deformation—measurable changes in the shape of the primary-ending terminals correlated with intrafusal sarcomere length, and what may cause them; (iv) putative stretch-sensitive channels—pharmacological and immunocytochemical clues to their identity; and (v) synaptic-like vesicles—the physiology and pharmacology of an intrinsic glutamatergic system in the primary and other mechanosensory endings, with some thoughts on the possible role of the system. Thus, the review highlights spindle stretch-evoked output is the product of multi-ionic receptor currents plus complex and sophisticated regulatory gain controls, both positive and negative in nature, as befits its status as the most complex sensory organ after the special senses.

The sensory innervation of cat hindlimb muscle spindles was studied by reconstruction, electron microscopy, and examination of teased, silver preparations to ascertain the form of the terminals and their distribution to bag1 (b1), bag2 (b2), and chain (c) muscle fibres. Reconstructions were made of two primary endings, one secondary ending, and the branching of four primary and six secondary axons. For the silver analysis spindles were teased from 14 different hindlimb muscles, the largest samples being from tenuissimus, peroneus brevis, p. longus, p. tertius, superficial lumbrical, extensor digitorum longus, and soleus. Among 310 spindles examined, 40 lacked a b1 fibre. These were all portions of tandem spindles in which the b2 fibre was continuous from one capsule, where it was accompanied by b1 and c fibres, to another, in which it was accompanied by c fibres only. These have been designated ‘b2c spindle units’ as distinct from ‘b1b2c spindle units’.

Fifty‐nanometre diameter, clear, synaptic‐like vesicles (SLVs) are found in primary mechanosensory nerve terminals of vertebrate and invertebrate animals. We have investigated their role in mechanosensory function using the muscle spindle primary endings of rat Ia afferents as a model. Uptake and release of the synaptic vesicle marker FM1‐43 indicated that SLVs recycle like synaptic vesicles and do so in a Ca²⁺‐sensitive manner. Mechanical stimulation increased SLV recycling, increasing both dye uptake and release. Immunogold/electronmicroscopy showed that, like the central synaptic endings, Ia peripheral endings are enriched with glutamate. Moreover, exogenous glutamate enhanced stretch‐induced Ia excitability. Enhanced excitability persisted in the presence of antagonists to the commonest ionotropic and metabotropic glutamate receptors (kynurenate, MCPG, CPPG and MAP4). However, excitation by glutamate was abolished by (R,S)‐3,5‐dihydroxyphenylglycine (DHPG), and rather more effectively by (2R,1′‐S,2′‐R,3′‐S)‐2‐(2′‐carboxy‐3′‐phenylcyclopropyl) glycine (PCCG‐13). PCCG‐13 also significantly reduced stretch‐activated excitability in the absence of exogenous glutamate. These data indicate that SLVs recycle at rest, releasing glutamate, and that mechanical activity increases this process. The blockade with DHPG and PCCG‐13 suggests that endogenous glutamate release acts, at least in part, through the recently described phospholipase D‐linked metabotropic Glu receptor to maintain the excitability of the sensory endings.