Pharmacological evidence that endogenous ATP modulates cochlear mechanics

Skellett, Ruth A; Chen, Chu; Fallon, Maureen; Nenov, Anastas P.; Bobbin, Richard P.

doi:10.1016/s0378-5955(97)00093-2

Cited by 34 publications

(24 citation statements)

References 39 publications

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“…Patch-clamp experiments revealed that extracellular application of 5-10 lM ATP to OHCs induces an inward current that is reduced by both purinergic receptor antagonists, suramin (100 lM) and cibacron blue (100 lM; Skellet et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Differential expression of purinergic receptor subtypes in the outer hair cells of the guinea pig

et al. 2004

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Section: Introductionmentioning

confidence: 99%

Differential expression of purinergic receptor subtypes in the outer hair cells of the guinea pig

et al. 2004

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“…Many in vivo studies of drugs that cause reversible cochlear dysfunction have been performed. These include changing the extracochlear efferent activity on the cochlea (Bobbin and Konishi, 1971;Bobbin and Konishi, 1974;Konishi, 1972;Kujawa et al, 1992b;Yoshida et al, 1999;Yoshida et al, 2001;Zheng et al, 2000), inhibiting the endolymphatic potential (Chen et al, 1995;Ruggero and Rich, 1991;Sewell, 1984;Ueda et al, 1992), and affecting intracellular targets within the OHC (Fitzgerald et al, 1993;Kujawa et al, 1992a;Laurikainen et al, 1997;Puel et al, 1990;Skellett et al, 1997). The best example of a drug in the last category that has been characterized thoroughly both in vitro and in vivo is salicylate.…”

Section: Introductionmentioning

confidence: 99%

Chlorpromazine inhibits cochlear function in guinea pigs

Oghalai¹

2004

Hearing Research

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“…ATP is another potential neuromodulator of the electrical activity of SGNs. Indeed, experimental perfusion of the cochlea in vivo with ATP or analogs has also shown a significant influence on neural thresholds (5,34,60). Calcium mobilization via metabotropic P2Y receptors (7) and membrane depolarization via ionotropic P2X receptors have been shown in isolated SGNs (53).…”

mentioning

confidence: 99%

Nonselective cation conductance activated by muscarinic and purinergic receptors in rat spiral ganglion neurons

Ito

Dulon

2002

American Journal of Physiology-Cell Physiology

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Ito, Ken, and Didier Dulon. Nonselective cation conductance activated by muscarinic and purinergic receptors in rat spiral ganglion neurons. Am J Physiol Cell Physiol 282: C1121-C1135, 2002. First published December 19, 2001 10.1152/ajpcell.00364.2001.-The present study characterizes the ionic conductances activated by acetylcholine (ACh) and ATP, two candidate neuromodulators, in isolated spiral ganglion neurons (SGNs). Brief application (1 s) of ACh evoked in a dose-dependent manner (EC50 ϭ 4.1 M) a reversible inward current with a long latency (average 1.3 s), at holding potential (Vh) ϭ Ϫ50 mV. This current was reversibly blocked by atropine and mimicked by muscarine. Application of ATP also evoked a reversible inward current at V h ϭ Ϫ50 mV, but the current showed two components. A fast component with a short latency was largely reduced when N-methyl-D-glucamine (NMDG) replaced extracellular sodium, implying a P2X-like ionotropic conductance. The second component had a longer latency (average 1.1 s) and was presumably activated by metabotropic P2Y-like receptors. The second component of ATP-evoked current shared similar characteristics with the responses evoked by ACh: the current reversed near 0 mV, displayed inward rectification, could be carried by NMDG, and was insensitive to extracellular and intracellular calcium. This ACh-/ATP-evoked conductance was reversibly inhibited by preapplication of ionomycin. These results suggest that muscarinic receptors and purinergic metabotropic receptors activate a similar large nonselective cation conductance via a common intracellular pathway in SGNs, a candidate mechanism to regulate neuronal excitability of SGNs.acetylcholine; adenosine 5Ј-triphosphate; cochlear neuron SPIRAL GANGLION NEURONS (SGNs) are peripheral bipolar neurons located in the cochlea that convey to the brain stem the acoustic information arising from the mechanoelectrical transduction of the inner hair cells (IHCs). The dendrites of SGNs below IHCs are contacted by efferent fibers that originate from small central neurons in the lateral superior olive. This lateral efferent innervation from the brain stem has long been suggested as a central control of the auditory nerve activity at the periphery [for review, see Warr (70)]. However, efferent regulation of SGN excitability still remains largely unexplored.Several immunocytochemical studies have suggested that acetylcholine (ACh) could be one of the main neurotransmitters present at these lateral efferent synapses [for review, see Eybalin (15)]. On the other hand, microiontophoresis of ACh in the subsynaptic area below IHCs in vivo has been shown to increase the subsynaptic spiking activity of the afferent nerve fibers (18), thus suggesting an excitatory regulation by ACh. However, the type of cholinergic receptors involved at these lateral efferent synapses is still debated, because mRNA expression of both muscarinic (12, 52) and nicotinic (44) receptors has been reported in SGNs. Recently, our laboratory demonstrated (50) the presence of functi...

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Pharmacological evidence that endogenous ATP modulates cochlear mechanics

Cited by 34 publications

References 39 publications

Differential expression of purinergic receptor subtypes in the outer hair cells of the guinea pig

Differential expression of purinergic receptor subtypes in the outer hair cells of the guinea pig

Chlorpromazine inhibits cochlear function in guinea pigs

Nonselective cation conductance activated by muscarinic and purinergic receptors in rat spiral ganglion neurons

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