Limits...
Mechanotransduction in the muscle spindle.

Bewick GS, Banks RW - Pflugers Arch. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK, g.s.bewick@abdn.ac.uk.

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.

Show MeSH

Related in: MedlinePlus

a–d Progressive geometrical abstraction of a single terminal of a spindle primary ending, leading to a flow-chart summarising the events of mechanosensory transduction. Green block arrows in (a–c) indicate the direction and distribution of stretch applied to the terminal when the primary ending is lengthened during muscle stretch or fusimotor stimulation. a A single terminal in its annulospiral form, taken from a primary ending reconstructed from serial sections [8]. Several such terminals typically enclose a single intrafusal muscle fibre. The terminal is connected to its associated heminode by a short, unmyelinated preterminal axonal branch at the point shown. b The terminal unrolled and turned through 90°. Note that individual terminals may be repeatedly branched and that the direction of stress during stretch is orthogonal to the long axis of the terminal. c A terminal and its associated unmyelinated preterminal branch shown in abstract cylindrical form to indicate the relative diameters of these structures. The smaller preterminal branch to the right is about 1 μm diameter. The lengths, especially that of the much larger terminal to the left, are highly variable. d Flow chart to illustrate the main events of mechanosensory transduction, as described in this review. The principal feed-forward pathway from stimulus (stretch) to output (action potentials) is shown by the white block arrows. We envisage that the overall gain of this pathway is controlled by several feedback pathways: negative feedback 1 is at present hypothetical and is included to account for the reversible silencing of the primary ending by PCCG-13 inhibition of the PLD-linked mGluR; the positive feedback pathway is the well-established SLV/glutamatergic loop; negative feedbacks 2 and 3 involve different kinds of K[Ca], one located in the terminal, the other in the heminode and both perhaps triggered by action potentials opening voltage-gated Ca channels. Green lines and arrowheads indicate enhancing/excitatory actions; red lines and circles indicate reducing/inhibitory actions
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4281366&req=5

Fig10: a–d Progressive geometrical abstraction of a single terminal of a spindle primary ending, leading to a flow-chart summarising the events of mechanosensory transduction. Green block arrows in (a–c) indicate the direction and distribution of stretch applied to the terminal when the primary ending is lengthened during muscle stretch or fusimotor stimulation. a A single terminal in its annulospiral form, taken from a primary ending reconstructed from serial sections [8]. Several such terminals typically enclose a single intrafusal muscle fibre. The terminal is connected to its associated heminode by a short, unmyelinated preterminal axonal branch at the point shown. b The terminal unrolled and turned through 90°. Note that individual terminals may be repeatedly branched and that the direction of stress during stretch is orthogonal to the long axis of the terminal. c A terminal and its associated unmyelinated preterminal branch shown in abstract cylindrical form to indicate the relative diameters of these structures. The smaller preterminal branch to the right is about 1 μm diameter. The lengths, especially that of the much larger terminal to the left, are highly variable. d Flow chart to illustrate the main events of mechanosensory transduction, as described in this review. The principal feed-forward pathway from stimulus (stretch) to output (action potentials) is shown by the white block arrows. We envisage that the overall gain of this pathway is controlled by several feedback pathways: negative feedback 1 is at present hypothetical and is included to account for the reversible silencing of the primary ending by PCCG-13 inhibition of the PLD-linked mGluR; the positive feedback pathway is the well-established SLV/glutamatergic loop; negative feedbacks 2 and 3 involve different kinds of K[Ca], one located in the terminal, the other in the heminode and both perhaps triggered by action potentials opening voltage-gated Ca channels. Green lines and arrowheads indicate enhancing/excitatory actions; red lines and circles indicate reducing/inhibitory actions

Mentions: Of course, a positive feedback gain control, operating in isolation, would make spindle outputs very unstable, particularly during times of intensive activity. A negative feedback control must also be present to overcome this tendency (Fig. 10). This seems to involve a combination of Ca2+ and K[Ca] channels [47, 55, 79], some of which may contribute to the receptor potential itself [40] (Shenton et al., unpublished data), as described in a previous section. Normal activity would activate the voltage-gated Ca2+ channels, thereby opening the K+ channels and reducing firing. Finally, these complex control systems seem likely to be confined to different loci as protein complexes and also tethered to cytoskeletal elements. We are now exploring one such binding protein, the PDZ-scaffold protein Whirlin. We have recently shown a mutation in Whirlin, which is responsible for the deaf/blindness of Usher’s syndrome, selectively impairs stretch-evoked responsiveness in muscle spindles [23].Fig. 10


Mechanotransduction in the muscle spindle.

Bewick GS, Banks RW - Pflugers Arch. (2014)

a–d Progressive geometrical abstraction of a single terminal of a spindle primary ending, leading to a flow-chart summarising the events of mechanosensory transduction. Green block arrows in (a–c) indicate the direction and distribution of stretch applied to the terminal when the primary ending is lengthened during muscle stretch or fusimotor stimulation. a A single terminal in its annulospiral form, taken from a primary ending reconstructed from serial sections [8]. Several such terminals typically enclose a single intrafusal muscle fibre. The terminal is connected to its associated heminode by a short, unmyelinated preterminal axonal branch at the point shown. b The terminal unrolled and turned through 90°. Note that individual terminals may be repeatedly branched and that the direction of stress during stretch is orthogonal to the long axis of the terminal. c A terminal and its associated unmyelinated preterminal branch shown in abstract cylindrical form to indicate the relative diameters of these structures. The smaller preterminal branch to the right is about 1 μm diameter. The lengths, especially that of the much larger terminal to the left, are highly variable. d Flow chart to illustrate the main events of mechanosensory transduction, as described in this review. The principal feed-forward pathway from stimulus (stretch) to output (action potentials) is shown by the white block arrows. We envisage that the overall gain of this pathway is controlled by several feedback pathways: negative feedback 1 is at present hypothetical and is included to account for the reversible silencing of the primary ending by PCCG-13 inhibition of the PLD-linked mGluR; the positive feedback pathway is the well-established SLV/glutamatergic loop; negative feedbacks 2 and 3 involve different kinds of K[Ca], one located in the terminal, the other in the heminode and both perhaps triggered by action potentials opening voltage-gated Ca channels. Green lines and arrowheads indicate enhancing/excitatory actions; red lines and circles indicate reducing/inhibitory actions
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4281366&req=5

Fig10: a–d Progressive geometrical abstraction of a single terminal of a spindle primary ending, leading to a flow-chart summarising the events of mechanosensory transduction. Green block arrows in (a–c) indicate the direction and distribution of stretch applied to the terminal when the primary ending is lengthened during muscle stretch or fusimotor stimulation. a A single terminal in its annulospiral form, taken from a primary ending reconstructed from serial sections [8]. Several such terminals typically enclose a single intrafusal muscle fibre. The terminal is connected to its associated heminode by a short, unmyelinated preterminal axonal branch at the point shown. b The terminal unrolled and turned through 90°. Note that individual terminals may be repeatedly branched and that the direction of stress during stretch is orthogonal to the long axis of the terminal. c A terminal and its associated unmyelinated preterminal branch shown in abstract cylindrical form to indicate the relative diameters of these structures. The smaller preterminal branch to the right is about 1 μm diameter. The lengths, especially that of the much larger terminal to the left, are highly variable. d Flow chart to illustrate the main events of mechanosensory transduction, as described in this review. The principal feed-forward pathway from stimulus (stretch) to output (action potentials) is shown by the white block arrows. We envisage that the overall gain of this pathway is controlled by several feedback pathways: negative feedback 1 is at present hypothetical and is included to account for the reversible silencing of the primary ending by PCCG-13 inhibition of the PLD-linked mGluR; the positive feedback pathway is the well-established SLV/glutamatergic loop; negative feedbacks 2 and 3 involve different kinds of K[Ca], one located in the terminal, the other in the heminode and both perhaps triggered by action potentials opening voltage-gated Ca channels. Green lines and arrowheads indicate enhancing/excitatory actions; red lines and circles indicate reducing/inhibitory actions
Mentions: Of course, a positive feedback gain control, operating in isolation, would make spindle outputs very unstable, particularly during times of intensive activity. A negative feedback control must also be present to overcome this tendency (Fig. 10). This seems to involve a combination of Ca2+ and K[Ca] channels [47, 55, 79], some of which may contribute to the receptor potential itself [40] (Shenton et al., unpublished data), as described in a previous section. Normal activity would activate the voltage-gated Ca2+ channels, thereby opening the K+ channels and reducing firing. Finally, these complex control systems seem likely to be confined to different loci as protein complexes and also tethered to cytoskeletal elements. We are now exploring one such binding protein, the PDZ-scaffold protein Whirlin. We have recently shown a mutation in Whirlin, which is responsible for the deaf/blindness of Usher’s syndrome, selectively impairs stretch-evoked responsiveness in muscle spindles [23].Fig. 10

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK, g.s.bewick@abdn.ac.uk.

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.

Show MeSH
Related in: MedlinePlus