scholarly journals Mechanotransduction and hyperpolarization-activated currents contribute to spontaneous activity in mouse vestibular ganglion neurons

2014 ◽  
Vol 143 (4) ◽  
pp. 481-497 ◽  
Author(s):  
Geoffrey C. Horwitz ◽  
Jessica R. Risner-Janiczek ◽  
Jeffrey R. Holt
Keyword(s):  
Hair Cell ◽  
Spontaneous Activity ◽  
Action Potentials ◽  
Ex Vivo ◽  
Vestibular Neuron ◽  
Vestibular Ganglion ◽  
Vestibular Hair Cells ◽  
Reverse Transcription Pcr ◽  
Current Clamp Mode ◽  
Ganglion Neurons

The hyperpolarization-activated, cyclic nucleotide–sensitive current, Ih, is present in vestibular hair cells and vestibular ganglion neurons, and is required for normal balance function. We sought to identify the molecular correlates and functional relevance of Ih in vestibular ganglion neurons. Ih is carried by channels consisting of homo- or heteromeric assemblies of four protein subunits from the Hcn gene family. The relative expression of Hcn1–4 mRNA was examined using a quantitative reverse transcription PCR (RT-PCR) screen. Hcn2 was the most highly expressed subunit in vestibular neuron cell bodies. Immunolocalization of HCN2 revealed robust expression in cell bodies of all vestibular ganglion neurons. To characterize Ih in vestibular neuron cell bodies and at hair cell–afferent synapses, we developed an intact, ex vivo preparation. We found robust physiological expression of Ih in 89% of cell bodies and 100% of calyx terminals. Ih was significantly larger in calyx terminals than in cell bodies; however, other biophysical characteristics were similar. Ih was absent in calyces lacking Hcn1 and Hcn2, but small Ih was still present in cell bodies, which suggests expression of an additional subunit, perhaps Hcn4. To determine the contributions of hair cell mechanotransduction and Ih to the firing patterns of calyx terminals, we recorded action potentials in current-clamp mode. Mechanotransduction currents were modulated by hair bundle defection and application of calcium chelators to disrupt tip links. Ih activity was modulated using ZD7288 and cAMP. We found that both hair cell transduction and Ih contribute to the rate and regularity of spontaneous action potentials in the vestibular afferent neurons. We propose that modulation of Ih in vestibular ganglion neurons may provide a mechanism for modulation of spontaneous activity in the vestibular periphery.

scholarly journals Sustained Loss of Bdnf Affects Peripheral but Not Central Vestibular Targets

2021 ◽  
Vol 12 ◽  
Author(s):  
Karen L. Elliott ◽  
Jennifer Kersigo ◽  
Jeong Han Lee ◽  
Ebenezer N. Yamoah ◽  
Bernd Fritzsch
Keyword(s):  
Vestibular System ◽  
Hair Cells ◽  
Molecular Mechanisms ◽  
Vestibular Nucleus ◽  
Target Cells ◽  
Central Target ◽  
Vestibular Ganglion ◽  
Vestibular Hair Cells ◽  
Ganglion Neurons

The vestibular system is vital for proper balance perception, and its dysfunction contributes significantly to fall-related injuries, especially in the elderly. Vestibular ganglion neurons innervate vestibular hair cells at the periphery and vestibular nuclei and the uvula and nodule of the cerebellum centrally. During aging, these vestibular ganglion neurons degenerate, impairing vestibular function. A complete understanding of the molecular mechanisms involved in neurosensory cell survival in the vestibular system is unknown. Brain-derived neurotrophic factor (BDNF) is specifically required for the survival of vestibular ganglion neurons, as its loss leads to early neuronal death. Bdnf null mice die within 3 weeks of birth, preventing the study of the long-term effects on target cells. We use Pax2-cre to conditionally knock out Bdnf, allowing mice survival to approximately 6 months of age. We show that a long-term loss of Bdnf leads to a significant reduction in the number of vestibular ganglion neurons and a reduction in the number of vestibular hair cells. There was no significant decrease in the central targets lateral vestibular nucleus (LVN) or the cerebellum at 6 months. This suggests that the connectivity between central target cells and other neurons suffices to prevent their loss despite vestibular hair cell and ganglion neuron loss. Whether the central neurons would undergo eventual degeneration in the absence of Bdnf remains to be determined.

scholarly journals Identification and modelling of fast and slow I h current components in vestibular ganglion neurons

2015 ◽  
Vol 42 (10) ◽  
pp. 2867-2877 ◽  
Author(s):  
Christophe B. Michel ◽  
Christine Azevedo Coste ◽  
Gilles Desmadryl ◽  
Jean‐Luc Puel ◽  
Jerome Bourien ◽  
...  
Keyword(s):  
Vestibular Ganglion ◽  
Ganglion Neurons

Axotomy- and Autotomy-Induced Changes in the Excitability of Rat Dorsal Root Ganglion Neurons

2001 ◽  
Vol 85 (2) ◽  
pp. 630-643 ◽  
Author(s):  
Fuad A. Abdulla ◽  
Peter A. Smith
Keyword(s):  
Sciatic Nerve ◽  
Dorsal Root Ganglion ◽  
Spontaneous Activity ◽  
Dorsal Root ◽  
Sensory Nerves ◽  
Dorsal Root Ganglion Neurons ◽  
Small Cells ◽  
Resting Membrane Potential ◽  
Ganglion Neurons ◽  
Induced Changes

The spontaneous, ectopic activity in sensory nerves that is induced by peripheral nerve injury is thought to contribute to the generation of “neuropathic” pain in humans. To examine the cellular mechanisms that underlie this activity, neurons in rat L4–L5 dorsal root ganglion (DRG) were first grouped as “large,” “medium,” or “small” on the basis of their size (input capacitance) and action potential (AP) shape. A fourth group of cells that exhibited a pronounced afterdepolarization (ADP) were defined as AD-cells. Whole cell recording was used to compare the properties of control neurons with those dissociated from rats in which the sciatic nerve had been sectioned (“axotomy” group) and with neurons from rats that exhibited self-mutilatory behavior in response to sciatic nerve section (“autotomy” group). Increases in excitability in all types of DRG neuron were seen within 2–7 wk of axotomy. Resting membrane potential (RMP) and the amplitude and duration of the afterhyperpolarization (AHP) that followed the AP were unaffected. Effects of axotomy were greatest in the small, putative nociceptive cells and least in the large cells. Moderate changes were seen in the medium and AD-cells. Compared to control neurons, axotomized neurons exhibited a higher frequency of evoked AP discharge in response to 500-ms depolarizing current injections; i.e., “gain” was increased and accommodation was decreased. The minimum current required to discharge an AP (rheobase) was reduced. There were significant increases in spike width in small cells and significant increases in spike height in small, medium, and AD-cells. The electrophysiological changes promoted by axotomy were intensified in animals that exhibited autotomy; spike height, and spike width were significantly greater than control for all cell types. Under our experimental conditions, spontaneous activity was never encountered in neurons dissociated from animals that exhibited autotomy. Thus changes in the electrical properties of cell bodies alone may not entirely account for injury-induced spontaneous activity in sensory nerves. The onset of autotomy coincided with alterations in the excitability of large, putative nonnociceptive, neurons. Thus large cells from the autotomy group were muchmore excitable than those from the axotomy group, whereas small cells from the autotomy group were only slightly more excitable. This is consistent with the hypothesis that the onset of autotomy is associated with changes in the properties of myelinated fibers. Changes in Ca2+ and K+ channel conductances that contribute to axotomy- and autotomy-induced changes in excitability are addressed in the accompanying paper.

Membrane resistance increases when automaticity develops in explanted rat heart cells

1990 ◽  
Vol 258 (1) ◽  
pp. H145-H152 ◽  
Author(s):  
O. F. Schanne ◽  
M. Lefloch ◽  
B. Fermini ◽  
E. Ruiz-Petrich
Keyword(s):  
Spontaneous Activity ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Input Resistance ◽  
Membrane Resistance ◽  
Resting Potential ◽  
Heart Cells ◽  
Membrane Capacity ◽  
Rat Heart Cells ◽  
Specific Membrane

We compared the passive electrical properties of isolated ventricular myocytes (resting potential -65 mV, fast action potentials, and no spontaneous activity) with those of 2- to 7-day-old cultured ventricle cells from neonatal rats (resting potential -50 mV, slow action potentials, and presence of spontaneous activity). In myocytes the specific membrane capacity was 0.99 microF/cm2, and the specific membrane resistance increased from 2.46 k omega.cm2 at -65 mV to 7.30 k omega.cm2 at -30 mV. In clusters, the current-voltage relationships measured under current-clamp conditions showed anomalous rectification and the input resistance decreased from 1.05 to 0.48 M omega when external K+ concentration was increased from 6 to 100 mM. Using the model of a finite disk we determined the specific membrane resistance (12.9 k omega.cm2), the effective membrane capacity (17.8 microF/cm2), and the lumped resistivity of the disk interior (1,964 omega.cm). We conclude that 1) the voltage dependence of the specific membrane resistance cannot completely explain the membrane resistance increase that accompanies the appearance of spontaneous activity; 2) a decrease of the inwardly rectifying conductance (gk1) is mainly responsible for the increase in the specific membrane resistance and depolarization; and 3) approximately 41% of the inward-rectifying channels are electrically silent when spontaneous activity develops in explanted ventricle cells.

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