Purinergic signaling in cochleovestibular hair cells and afferent neurons

Ito, Ken; Dulon, Didier

doi:10.1007/s11302-010-9183-x

Cited by 11 publications

(10 citation statements)

References 75 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that both inner and outer hair cells express P2X 2 which mediate ATP-induced cationic currents (Housley et al, 1999;Järlebark et al, 2002). We found no expression of P2X 2 in the spiral ganglionic afferents that innervate the inner and outer hair cells, in disagreement with some immunohistochemical studies and dissociated patch clamp studies (Järlebark et al, 2002;Weisz et al, 2009;Ito and Dulon, 2010).…”

Section: Discussioncontrasting

confidence: 87%

Development of a Mouse Reporter Strain for the Purinergic P2X₂Receptor

Kim

Bahia

Patil

et al. 2020

eNeuro

View full text Add to dashboard Cite

The ATP-sensitive P2X 2 ionotropic receptor plays a critical role in a number of signal processes including taste and hearing, carotid body detection of hypoxia, the exercise pressor reflex and sensory transduction of mechanical stimuli in the airways and bladder. Elucidation of the role of P2X 2 has been hindered by the lack of selective tools. In particular, detection of P2X 2 using established pharmacological and biochemical techniques yields dramatically different expression patterns, particularly in the peripheral and central nervous systems. Here, we have developed a knockin P2X 2-cre mouse, which we crossed with a cre-sensitive tdTomato reporter mouse to determine P2X 2 expression. P2X 2 was found in more than 80% of nodose vagal afferent neurons, but not in jugular vagal afferent neurons. Reporter expression correlated in vagal neurons with sensitivity to mATP. P2X 2 was expressed in 75% of petrosal afferents, but only 12% and 4% of dorsal root ganglia and trigeminal afferents, respectively. P2X 2 expression was limited to very few cell types systemically. Together with the central terminals of P2X 2expressing afferents, reporter expression in the CNS was mainly found in brainstem neurons projecting mossy fibers to the cerebellum, with little expression in the hippocampus or cortex. The structure of peripheral terminals of P2X 2-expressing afferents was demonstrated in the tongue (taste buds), carotid body, trachea and esophagus. P2X 2 was observed in hair cells and support cells in the cochlear, but not in spiral afferent neurons. This mouse strain provides a novel approach to the identification and manipulation of P2X 2-expressing cell types. 3 Significance statement Inhibitor and knockout studies have demonstrated the critical role of P2X 2 in multiple sensory signaling pathways. Nevertheless, P2X 2 expression patterns are controversial, as biochemical studies suggest widespread expression whereas functional studies suggest restricted expression. Functional characterization is further complicated by heteromeric P2X 2/3 channels that have hybrid pharmacology and biophysical properties. We have developed a P2X 2-cre mouse to determine the expression pattern of P2X 2. In the periphery, P2X 2 expression is found in almost all nodose sensory afferents but is limited to only minor subsets of trigeminal and DRG afferents. Centrally, P2X 2 is mostly expressed in neurons projecting mossy fibers to the cerebellum. Thus we provide novel evidence for the specific expression of P2X 2 , which is more limited than previously thought.

show abstract

Section: Discussioncontrasting

confidence: 87%

Development of a Mouse Reporter Strain for the Purinergic P2X₂Receptor

Kim

Bahia

Patil

et al. 2020

eNeuro

View full text Add to dashboard Cite

show abstract

“…IHCs in the pre-hearing cochlea also express P2 receptors (Huang et al, 2010; Ito and Dulon, 2010) (Figure S4) and spontaneous depolarizations of IHCs are sensitive to P2 receptor antagonists (Tritsch et al, 2007). To assess whether K + release from ISCs is sufficient to depolarize IHCs without purinergic receptor activation, we activated TMEM16A directly by inducing a rise in intracellular Ca 2+ within ISCs.…”

Section: Resultsmentioning

confidence: 99%

Spontaneous Activity of Cochlear Hair Cells Triggered by Fluid Secretion Mechanism in Adjacent Support Cells

Wang

Lin

Cheung

et al. 2015

Cell

120

205

View full text Add to dashboard Cite

Summary Spontaneous electrical activity of neurons in developing sensory systems promotes their maturation and proper connectivity. In the auditory system, spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from glia-like inner supporting cells (ISCs), facilitating maturation of central pathways before hearing onset. Here, we find that ATP stimulates purinergic autoreceptors in ISCs, triggering Cl− efflux and osmotic cell shrinkage by opening TMEM16A Ca2+-activated Cl− channels. Release of Cl− from ISCs also forces K+ efflux, causing transient depolarization of IHCs near ATP release sites. Genetic deletion of TMEM16A markedly reduces the spontaneous activity of IHCs and spiral ganglion neurons in the developing cochlea, and prevents ATP-dependent shrinkage of supporting cells. These results indicate that support cells in the developing cochlea have adapted a pathway used for fluid secretion in other organs to induce periodic excitation of hair cells.

show abstract

“…While there has been an extensive analysis of P2X receptor expression both in the developing and mature cochlea across several species (for reviews, see [1,22]), and adenosine receptor and ecto-nucleotidase activity has been established [23][24][25]. The sites and mechanisms of action of P2Y receptor activity in the cochlea are still emerging.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of P2Y receptors in the rat cochlea during development

Huang

Thorne

Vlajkovic

et al. 2010

Purinergic Signalling

View full text Add to dashboard Cite

Purinergic signaling has broad physiological significance to the hearing organ, involving signal transduction via ionotropic P2X receptors and metabotropic G-protein-coupled P2Y and P1 (adenosine), alongside conversion of nucleotides and nucleosides by ectonucleotidases and ecto-nucleoside diphosphokinase. In addition, ATP release is modulated by acoustic overstimulation or stress and involves feedback regulation. Many of these principal elements of the purinergic signaling complex have been well characterized in the cochlea, while the characterization of P2Y receptor expression is emerging. The present study used immunohistochemistry to evaluate the expression of five P2Y receptors, P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , and P2Y 12 , during development of the rat cochlea. Commencing in the late embryonic period, the P2Y receptors studied were found in the cells lining the cochlear partition, associated with establishment of the electrochemical environment which provides the driving force for sound transduction. In addition, early postnatal P2Y 2 and P2Y 4 protein expression in the greater epithelial ridge, part of the developing hearing organ, supports the view that initiation and regulation of spontaneous activity in the hair cells prior to hearing onset is mediated by purinergic signaling. Sub-cellular compartmentalization of P2Y receptor expression in sensory hair cells, and diversity of receptor expression in the spiral ganglion neurons and their satellite cells, indicates roles for P2Y receptormediated Ca 2+ -signaling in sound transduction and auditory neuron excitability. Overall, the dynamics of P2Y receptor expression during development of the cochlea complement the other elements of the purinergic signaling complex and reinforce the significance of extracellular nucleotide and nucleoside signaling to hearing.

show abstract

Purinergic signaling in cochleovestibular hair cells and afferent neurons

Cited by 11 publications

References 75 publications

Development of a Mouse Reporter Strain for the Purinergic P2X₂Receptor

Development of a Mouse Reporter Strain for the Purinergic P2X₂Receptor

Spontaneous Activity of Cochlear Hair Cells Triggered by Fluid Secretion Mechanism in Adjacent Support Cells

Differential expression of P2Y receptors in the rat cochlea during development

Contact Info

Product

Resources

About

Purinergic signaling in cochleovestibular hair cells and afferent neurons

Cited by 11 publications

References 75 publications

Development of a Mouse Reporter Strain for the Purinergic P2X2Receptor

Development of a Mouse Reporter Strain for the Purinergic P2X2Receptor

Spontaneous Activity of Cochlear Hair Cells Triggered by Fluid Secretion Mechanism in Adjacent Support Cells

Differential expression of P2Y receptors in the rat cochlea during development

Contact Info

Product

Resources

About

Development of a Mouse Reporter Strain for the Purinergic P2X₂Receptor

Development of a Mouse Reporter Strain for the Purinergic P2X₂Receptor