Pharmacological modulation of transmitter release by inhibition of pressure-dependent potassium currents in vestibular hair cells

  title={Pharmacological modulation of transmitter release by inhibition of pressure-dependent potassium currents in vestibular hair cells},
  author={Thorsten Haasler and Georg Homann and Thien An Duong Dinh and Eberhard Jüngling and Martin Westhofen and Andreas Lückhoff},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
Vestibular vertigo may be induced by increases in the endolymphatic pressure that activate pressure-dependent K+ currents (IK,p) in vestibular hair cells. IK,p have been demonstrated to modulate transmitter release and are inhibited by low concentrations of cinnarizine. Beneficial effects against vestibular vertigo of cinnarizine have been attributed to its inhibition of calcium currents. Our aim was to determine the extent by which the inhibition of IK,p by cinnarizine may alter the voltage… 

The effect of pressure on potassium currents in the inner hair cells isolated from guinea-pig cochlea.

  • T. Kimitsuki
  • Biology, Medicine
    Acta neurobiologiae experimentalis
  • 2013
The effects of pressure exerted on potassium currents in acutely isolated inner hair cells of the guinea-pig cochlea are investigated using whole-cell voltage-clamp techniques and Gadolinium, a blocker of stretch-activated cation channels, did not influence pressure-dependent changes in potassium currents; however, cinnarizine blocked pressure- dependent changes inassium currents.

The Role of Ion Channels in Cellular Mechanotransduction of Hydrostatic Pressure

Pressure changes as small as 0.5 cm H2O (50 Pa) have been shown to modulate potassium currents in vestibular type II hair cells from guinea pig utricles, and investigations of these phenomena are continuing to improve understanding of pressure mechanotransduction.

A synaptic F-actin network controls otoferlin-dependent exocytosis in auditory inner hair cells

It is shown that a cage-shaped F-actin network is essential for maintaining a tight spatial organization of Cav1.3 Ca2+ channels at the synaptic ribbons of auditory inner hair cells and that this network directly influences the efficiency of otoferlin-dependent exocytosis.

LC-MS/MS method development and validation of an antihistaminic, calcium channel blocker, di-phenyl-methyl-piperazine group containing cinnarizine in human plasma with an application to BA/BE studies in Indian volunteer

T attempts were made to develop and validate a bioanalytical method for the determination and quantitation of the cinnarizine in human plasma by liquid chromatography-mass spectrometric method and the developed method was also applied to analyse the plasma samples of healthy human volunteers obtained from a comparative pharmacokinetic study of cinnARizine 25mg tablet dosage forms.

Cinnarizine: A Contemporary Review

Combination therapy of cinnarizine and/ or its combinations demonstrated a better safety profile than either of the mono-components, offering a viable therapeutic option in vertigo management.

Comparison of the Therapeutic Efficacy of a Fixed Low-Dose Combination of Cinnarizine and Dimenhydrinate with Betahistine in Vestibular Neuritis

The results showed that the fixed low-dose combination of cin-narizine and dimenhydrinate is an effective and well tolerated option for symptomatic treatment in unilateral VN and led to significant improvements in vertigo and ADL within the first week, and to a nearly complete recovery after 4 weeks.

Perspectives in vestibular diagnostics and therapy

  • A. Ernst
  • Medicine
    GMS current topics in otorhinolaryngology, head and neck surgery
  • 2011
These and related trends point into a medical future which is characterized by presbyvertigo as classical sign of the demographic changes ahead, by shortage of financial resources and a medico-legally over-regulated, even hostile environment for physicians in clinical medicine.

Comparison of Cinnarizine/Dimenhydrinate Fixed Combination with the Respective Monotherapies for Vertigo of Various Origins

The fixed combination of cinnarizine 20 mg/dimenhydrinate 40 mg was an effective and well tolerated treatment for patients with vestibular vertigo of central and/or peripheral origin and exceeded that of each of the equally dosed active substances given as monotherapy, leading to higher responder rates.

Hydrostatic pressure enhances mitomycin C induced apoptosis in urothelial carcinoma cells.

Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates.



Inhibition of voltage-gated calcium currents in type II vestibular hair cells by cinnarizine

It is concluded that these direct actions of cinnarizine on hair cells should be considered as molecular mechanisms contributing to therapeutic effects ofcinnarIZine in vertigo.

Effects of cinnarizine on calcium and pressure-dependent potassium currents in guinea pig vestibular hair cells

It is concluded that cinnarizine inhibits, by two mechanisms, pressure-induced currents that are sensitive to charybdotoxin and Ca2+.

Potassium currents induced by hydrostatic pressure modulate membrane potential and transmitter release in vestibular type II hair cells

It is concluded that pressure-dependent K+ currents may alter the voltage response of vestibular hair cells to an extent critical for Ca2+ currents and transmitter release and may contribute tovestibular dysfunction in Meniere’s disease.

Potassium currents in type II vestibular hair cells isolated from the guinea-pig's crista ampullaris

It is concluded that at least two potassium conductances are present, a delayed rectifier with a relatively fast inactivation and a calcium-dependent potassium current, which is mainly carried by potassium ions.

The metabotropic glutamate receptors of the vestibular organs

Surface charge and calcium channel saturation in bullfrog sympathetic neurons

The results suggest that the channel pore does bind Ba2+ in a saturable manner, but the current-[Ba2+]o relationship may be significantly affected by surface charge.

Histamine stimulated synaptosomal Ca2+ uptake through activation of calcium channels.

How Endolymph Pressure Modulates Semicircular Canal Primary Afferent Discharge

Results demonstrate that the semicircular canals are indeed sensitive to small changes in translabyrinthine pressure in addition to head‐movement‐related changes in transcupular pressure.

Transmission between type II hair cells and bouton afferents in the turtle posterior crista.

Comparison of the phases of synaptic and spike activity suggests that both presynaptic and postsynaptic mechanisms contribute to variations across afferents in the timing of spikes during sinusoidal stimulation.