Acid-Sensing Ionic Channels in the Rat Vestibular Endorgans and Ganglia

2006 ◽  
Vol 96 (3) ◽  
pp. 1615-1624 ◽  
Author(s):  
Francisco Mercado ◽  
Iván A. López ◽  
Dora Acuna ◽  
Rosario Vega ◽  
Enrique Soto
Keyword(s):  
Pain Perception ◽  
Ionic Current ◽  
Ionic Channels ◽  
Functional Expression ◽  
Current Response ◽  
Afferent Neurons ◽  
Peripheral Tissues ◽  
Vestibular Ganglion ◽  
Vestibular Endorgans ◽  
Ganglion Neurons

Acid-sensing ionic channels (ASICs) are members of the epithelial Na+ channel/degenerin (ENaC/DEG) superfamily. ASICs are widely distributed in the central and peripheral nervous system. They have been implicated in synaptic transmission, pain perception, and the mechanoreception in peripheral tissues. Our objective was to characterize proton-gated currents mediated by ASICs and to determine their immunolocation in the rat vestibular periphery. Voltage clamp of cultured afferent neurons from P7 to P10 rats showed a proton-gated current with rapid activation and complete desensitization, which was carried almost exclusively by sodium ions. The current response to protons (H+) has a pH0.5 of 6.2. This current was reversibly decreased by amiloride, gadolinium, lead, acetylsalicylic acid, and enhanced by FMRFamide and zinc, and negatively modulated by raising the extracellular calcium concentration. Functional expression of the current was correlated with smaller-capacitance neurons. Acidification of the extracellular pH generated action potentials in vestibular neurons, suggesting a functional role of ASICs in their excitability. Immunoreactivity to ASIC1a and ASIC2a subunits was found in small vestibular ganglion neurons and afferent fibers that run throughout the macula utricle and crista stroma. ASIC2b, ASIC3, and ASIC4 were expressed to a lesser degree in vestibular ganglion neurons. The ASIC1b subunit was not detected in the vestibular endorgans. No acid-pH–sensitive currents or ASIC immunoreactivity was found in hair cells. Our results indicate that proton-gated current is carried through ASICs and that ionic current activated by H+ contributes to shape the vestibular afferent neurons' response to its synaptic input.

scholarly journals Sodium channel diversity in the vestibular ganglion: NaV1.5, NaV1.8, and tetrodotoxin-sensitive currents

2016 ◽  
Vol 115 (5) ◽  
pp. 2536-2555 ◽  
Author(s):  
Xiao-Ping Liu ◽  
Julian R. A. Wooltorton ◽  
Sophie Gaboyard-Niay ◽  
Fu-Chia Yang ◽  
Anna Lysakowski ◽  
...  
Keyword(s):  
Time Course ◽  
Voltage Dependence ◽  
Afferent Neurons ◽  
Small Current ◽  
Primary Afferent Neurons ◽  
Primary Afferent ◽  
Voltage Range ◽  
Vestibular Ganglion ◽  
Potential Shape ◽  
Ganglion Neurons

Firing patterns differ between subpopulations of vestibular primary afferent neurons. The role of sodium (NaV) channels in this diversity has not been investigated because NaV currents in rodent vestibular ganglion neurons (VGNs) were reported to be homogeneous, with the voltage dependence and tetrodotoxin (TTX) sensitivity of most neuronal NaV channels. RT-PCR experiments, however, indicated expression of diverse NaV channel subunits in the vestibular ganglion, motivating a closer look. Whole cell recordings from acutely dissociated postnatal VGNs confirmed that nearly all neurons expressed NaV currents that are TTX-sensitive and have activation midpoints between −30 and −40 mV. In addition, however, many VGNs expressed one of two other NaV currents. Some VGNs had a small current with properties consistent with NaV1.5 channels: low TTX sensitivity, sensitivity to divalent cation block, and a relatively negative voltage range, and some VGNs showed NaV1.5-like immunoreactivity. Other VGNs had a current with the properties of NaV1.8 channels: high TTX resistance, slow time course, and a relatively depolarized voltage range. In two NaV1.8 reporter lines, subsets of VGNs were labeled. VGNs with NaV1.8-like TTX-resistant current also differed from other VGNs in the voltage dependence of their TTX-sensitive currents and in the voltage threshold for spiking and action potential shape. Regulated expression of NaV channels in primary afferent neurons is likely to selectively affect firing properties that contribute to the encoding of vestibular stimuli.

Neurobiology of pain in osteoarthritis

2016 ◽  
Author(s):  
Philip Mease
Keyword(s):  
Chronic Pain ◽  
Pain Perception ◽  
Functional Neuroimaging ◽  
Ionic Channels ◽  
Genetic Profile ◽  
Grey Matter Volume ◽  
Peripheral Sensitization ◽  
Pain Mechanisms ◽  
Peripheral Tissues ◽  
Inhibitory Function

Significant advances in our understanding of the neurobiology of pain in osteoarthritis (OA) have occurred in the last decade and are herein summarized. Pain is the predominant symptom of OA and occurs at multiple levels from non-cartilage peripheral tissues to spinal cord, and brain and back. At each level, nerve function is regulated by complex ionic channels, neuropeptide expression, and cytokine and chemokine activity. Previously considered a non-inflammatory condition, it is now recognized that cell proliferation and inflammatory cytokine production occurs in OA synovium, contributing to peripheral sensitization. Genetic profile influences nociceptive neuropeptide expression and thus, pain perception. Both peripheral and central sensitizing factors, including increased neuropeptide and microglial activity, lead to pain augmentation and persistence. Pain processing in brain centres such as the somatosensory cortex and insula are influenced by affective areas such as the amygdala. Descending receptor pathways through the midbrain to the dorsal horn, such as norepinephrine, serotonin, opioid, and cannabinoid, normally provide pain inhibitory function but this function may be diminished in chronic pain states such as OA, leading to allodynia and hyperalgesia. Functional neuroimaging has contributed to our understanding of the complex interplay of peripheral and central mechanisms. Recent evidence that grey matter volume decrease in chronic pain states may be reversible (e.g. after pain relief post OA hip arthroplasty) illuminates the potential for central neuroplasticity. Greater understanding of the neurobiology of OA pain provides evidence for therapeutic approaches that address peripheral and/or central pain mechanisms and provides a guide for future targeted pain therapeutics.

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

scholarly journals Functional expression pattern of P2X receptors in rat dorsal root ganglion neurons.

1999 ◽  
Vol 79 ◽  
pp. 110
Author(s):  
Shinya Ueno ◽  
Makoto Tsuda ◽  
Takeshi Katsuragi ◽  
Toshihiko Iwanaga ◽  
Kazuhide Inoue
Keyword(s):  
Dorsal Root Ganglion ◽  
Expression Pattern ◽  
Dorsal Root ◽  
Functional Expression ◽  
P2x Receptors ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

scholarly journals Kinetic models for stochastically modified ionic channels

2008 ◽  
Vol 13 (3) ◽  
Author(s):  
Aleksander Wozinski ◽  
Jan Iwaniszewski
Keyword(s):  
Pore Structure ◽  
Binding Site ◽  
Kinetic Models ◽  
Degrees Of Freedom ◽  
Ionic Current ◽  
Ionic Channels ◽  
Thermal Fluctuations ◽  
Kinetic Description ◽  
Channel Conductivity ◽  
Channel Properties

AbstractIonic channels form pores in biomembranes. These pores are large macromolecular structures. Due to thermal fluctuations of countless degrees-of-freedom of the biomembrane material, the actual form of the pores is permanently subject to modification. Furthermore, the arrival of an ion at the binding site can change this form by repolarizing the surrounding aminoacids. In any case the variations of the pore structure are stochastic. In this paper, we discuss the effect of such modifications on the channel conductivity. Applying a simple kinetic description, we show that stochastic variations in channel properties can significantly alter the ionic current, even leading to its substantial increase or decrease for the specific matching of some time-scales of the system.

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