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

  title={Inhibition of voltage-gated calcium currents in type II vestibular hair cells by cinnarizine},
  author={Sonja F. Arab and Philip D{\"u}wel and Eberhard Jüngling and Martin Westhofen and Andreas Lückhoff},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
Cinnarizine is pharmaceutically used in conditions with vestibular vertigo such as Meniere’s disease. It is thought to act on extra-vestibular targets. We hypothesized that cinnarizine, as a blocker of L-type Ca2+ channels, may directly target vestibular hair cells where Ca2+ currents are important for the mechano-electrical transduction and transmitter release. Our aim was to clarify whether cinnarizine affected voltage-dependent Ca2+ currents in vestibular type II hair cells. Such cells were… 
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+.
Pharmacological modulation of transmitter release by inhibition of pressure-dependent potassium currents in vestibular hair cells
It is concluded that cinnarizine, in pharmacologically relevant concentrations, enhances transmitter release in the presence of elevated hydrostatic pressure by an indirect mechanism, involving inhibition of IK,p, enhancing depolarization, and increasing the voltage-dependent activation of Ca2+ currents, without directly affecting Ca2- current.
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.
Cation Permeability of Voltage-Gated Hair Cell Ca2+ Channels of the Vertebrate Labyrinth
L channel gating is affected by the ion species permeating the channel, and its selectivity filter binds Ca2+ more strongly than that of R channel; furthermore, external Ca2- prevents nifedipine from perturbing the R selectivityfilter.
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.
Neuropharmacology of Vestibular System Disorders
Drugs acting on vestibular system have been grouped into two main categories according to their primary mechanisms of action: those with effects on neurotransmitters and neuromodulator receptors and those that act on voltage-gated ion channels.
Neuropharmacological basis of vestibular system disorder treatment.
The development of basic studies addressing drug actions at the molecular, cellular and systems level, combined with reliable and well controlled clinical trials, would provide the scientific basis for new strategies for the treatment of vestibular disorders.
No Effects of Anti-Motion Sickness Drugs on Vestibular Evoked Myogenic Potentials Outcome Parameters
  • R. Vanspauwen, Aurelie P. Weerts, F. Wuyts
  • Medicine, Biology
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
  • 2011
The absence of clinically significant effects can be explained by the predominant presence of the target receptors for the applied drugs in the medial vestibular nucleus, which receives the lowest grade of saccular projections.
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.
Efficacy and Safety of a Fixed Combination of Cinnarizine 20 mg and Dimenhydrinate 40 mg vs Betahistine Dihydrochloride 16 mg in Patients with Peripheral Vestibular Vertigo: A Prospective, Multinational, Multicenter, Double-Blind, Randomized, Non-inferiority Clinical Trial
Evidence is provided that the fixed-combination preparation is a potent and even superior alternative to betahistine in the treatment of vertigo related to peripheral vestibular vertigo.


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.
Voltage-gated calcium channel currents in type I and type II hair cells isolated from the rat crista.
The results lend credence to suggestions that type I cells have more positive resting potentials in vivo, possibly through K+ accumulation in the synaptic cleft or inhibition of the large K+ conductance.
Potassium depolarization of mammalian vestibular sensory cells increases [Ca2+]i through voltage‐sensitive calcium channels
Results provide the first direct evidence that L‐ and probably T‐type channels control the K+‐induced Ca2+ influx in both types of sensory cells.
Cav1.3 (α1D) Ca2+ Currents in Neonatal Outer Hair Cells of Mice
Ca2+ currents in outer hair cells aged between postnatal day 1 (P1) and P8 (P8) showed a rapidly activating inward current that was 1.8 times larger with 10 mm Ba2+ as charge carrier (IBa) than with equimolar Ca2+ (ICa) and single cell RT‐PCR revealed expression of Cav1.3 in OHCs.
Characterization of voltage-gated calcium currents in freshly isolated smooth muscle cells from rat tail main artery.
It is shown that smooth muscle cells freshly isolated from rat tail main artery may be divided into two populations, one expressing both L- and T- type and the other only L-type Ca2+ channels, and cinnarizine potently inhibited T-type currents at low concentrations but also blocked L- type Ca2+.
Two types of calcium channels in isolated smooth muscle cells from rat tail artery.
BAY K 8644 shifted the activation threshold, the peak inward current, and the steady-state inactivation-activation curves of L-type channel currents in the direction of hyperpolarization.