Mechanotransduction in the muscle spindle

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00424-014-1536-9) contains supplementary material, which is available to authorized users.

Complex impairment of IA muscle proprioceptors following traumatic or neurotoxic injury

“…The work of Bewick and Banks gives evidence for a glutamate-dependent autogenic excitatory mechanism (Fig. 6), which increases IA afferent firing (Bewick et al 2005; Bewick & Banks, 2014). It is reasonable then to speculate that riluzole reduces static firing by impeding glutamate signaling within the IA afferent terminal.…”

“…Receptor potential size and shape reflect different dynamic and static components of mechanical perturbations (Hunt & Ottoson, 1975). Recent evidence indicates that epithelial sodium channels may be responsible for the Na + current of the receptor potential (Simon et al 2010), but the channel responsible for Ca 2+ current has yet to be adequately characterized (Bewick & Banks, 2014). In the next step of peripheral signaling, the receptor potential spreads electronically to the unmyelinated heminode of the IA afferent terminal where its features are encoded in the firing pattern of action potentials generated by voltage-gated Na + and K + channels.…”

“…Firing is suppressed by negative feedback mechanisms initiated in the afferent terminal by action potentials that open P/Q-type Ca 2+ channels. The resulting Ca 2+ influx suppresses afferent firing by increasing K + current through large-conductance Ca 2+ -activated K + channels (BK) within the heminode (Kruse & Poppele, 1991; Simon et al 2008; Bewick & Banks, 2014), and through small-conductance Ca 2+ -activated K + channels (SK) located within the afferent terminal (Bewick & Banks, 2014; Shenton et al 2014). These mechanisms suppress afferent firing on a short time scale, for example, fractions of a second.…”

“…A separate intrinsic mechanism increases spindle firing and is essential for maintaining IA afferent responsiveness over a time course of minutes to hours. In this autogenic excitatory mechanism, synaptic-like vesicles in IA afferent annulosprinal endings are stimulated by Ca 2+ influx to exocytose glutamate, which binds to a phospholipase D-linked metabotropic glutamate receptor to activate second-messenger signaling that enhances afferent firing (Bewick et al 2005; Bewick & Banks, 2014). These mechanisms come into consideration below where we discuss the effects of chemotherapy on IA afferent firing.…”

A special issue on physiological aspects of mechanosensing

“…Essential forcetransducing channels have been identified in bacteria and invertebrate organisms [2,4,17]. Multiple mechanosensory protein complexes have also been described in cardiac myocytes [7], skeletal muscles [1], and vascular cells [12]. Although, the sensations of touch and hearing remain without a clear understanding of their molecular basis, we are now beginning to uncover molecular players that govern the mechanosensory functions of these receptors [3,4,6,8,10,11,13,16].…”