ArticleThe Journal of physiology2000
Gentamicin blocks ACh-evoked K+ current in guinea-pig outer hair cells by impairing Ca2+ entry at the cholinergic receptor.
Article in The Journal of physiology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 50 citations in OpenAlex.
- Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Mechanisms of Aminoglycoside- and Cisplatin-Induced Ototoxicity.American journal of audiology · 2021Review
- Aminoglycoside- and Cisplatin-Induced Ototoxicity: Mechanisms and Otoprotective Strategies.Cold Spring Harbor perspectives in medicine · 2019Review
- Protecting Mammalian Hair Cells from Aminoglycoside-Toxicity: Assessing Phenoxybenzamine's Potential.Frontiers in cellular neuroscience · 2017Article
- Aminoglycoside-Induced Cochleotoxicity: A Review.Frontiers in cellular neuroscience · 2017Review
- Local mechanisms for loud sound-enhanced aminoglycoside entry into outer hair cells.Frontiers in cellular neuroscience · 2015Article
- Gentamicin blocks the ACh-induced BK current in guinea pig type II vestibular hair cells by competing with Ca²⁺ at the L-type calcium channel.International journal of molecular sciences · 2014Article
- Extracellular gentamicin reduces the activity of connexin hemichannels and interferes with purinergic Ca(2+) signaling in HeLa cells.Frontiers in cellular neuroscience · 2014Article
- Antibiotic supplements affect electrophysiological properties and excitability of rat hippocampal pyramidal neurons in primary culture.Iranian biomedical journal · 2013Article
- TRPA1-mediated accumulation of aminoglycosides in mouse cochlear outer hair cells.Journal of the Association for Research in Otolaryngology : JARO · 2011Article
- Functional hair cell mechanotransducer channels are required for aminoglycoside ototoxicity.PloS one · 2011Article
- The efferent system or olivocochlear function bundle - fine regulator and protector of hearing perception.International journal of biomedical science : IJBS · 2010Article
- Aminoglycoside block of P2X2 receptors heterologously expressed in Xenopus laevis oocytes.Purinergic signalling · 2010Article
- Efferent pathways modulate hyperactivity in inferior colliculus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Effects of medial olivocochlear efferent stimulation on the activity of neurons in the auditory midbrain.Experimental brain research · 2008Article
- Gentamicin abolishes all cochlear effects of electrical stimulation of the inferior colliculus.Experimental brain research · 2006Article
- The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair cells through the mechano-electrical transducer channels.The Journal of physiology · 2005Article
- Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells.The Journal of physiology · 2005Article
- Pharmacology of acetylcholine-mediated cell signaling in the lateral line organ following efferent stimulation.Journal of neurophysiology · 2005Article
- The significance of the calcium signal in the outer hair cells and its possible role in tinnitus of cochlear origin.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2004Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aminoglycoside antibiotics such as gentamicin are known to block the medial olivocochlear efferent system. In order to determine whether this inhibition takes place at the postsynaptic cholinergic receptors in outer hair cells (OHCs), we studied the effects of these polycationic molecules on cholinergic currents evoked in isolated guinea-pig OHCs. The cholinergic response of OHCs involves nicotinic-like receptors (nAChRs) permeable to Ca2+ ions that activate nearby Ca2+-sensitive K+ channels (KCa(ACh) channels). The extracellular application of gentamicin and neomycin reversibly blocked ACh-evoked K+ current (IK(ACh)) with IC50 values of 5.5 and 3.2 microM, respectively. The results showed that the blocking mechanism of IK(ACh) was due to inhibition of Ca2+ influx via nAChRs. Our study also provides interesting insights into the functional coupling between nAChRs and KCa(ACh) channels in OHCs. By directly recording the cation current flowing through nAChRs (In(ACh)) using an intracellular solution containing 10 mM BAPTA, we measured an EC50 near 110 microM for ACh-evoked In(ACh). This EC50 for ACh is one order of magnitude higher than that measured indirectly on IK(ACh). This reveals a rather low affinity of ACh for its receptor but a very efficient coupling between nAChRs and KCa(ACh) channels. We also show that a high external Ca2+ concentration reverts the gentamicin inhibition of IK(ACh) and that gentamicin directly alters the cation current flowing through the nAChRs of OHCs. We propose that gentamicin acts as a non-competitive cholinergic blocker by displacing Ca2+ from specific binding sites at the nAChRs. This block of the nAChRs at the level of the postsynaptic membrane in OHCs could explain the inhibitory effect of gentamicin reported on the crossed medial olivocochlear efferent system in vivo.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.