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

@article{Dwel2005EffectsOC,
  title={Effects of cinnarizine on calcium and pressure-dependent potassium currents in guinea pig vestibular hair cells},
  author={Philip D{\"u}wel and Thorsten Haasler and Eberhard Jüngling and T Duong and Martin Westhofen and Andreas Lückhoff},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  year={2005},
  volume={371},
  pages={441-448}
}
In vestibular hair cells, K+ currents induced by rises in hydrostatic pressure have recently been demonstrated. These currents are inhibited by charybdotoxin, a blocker of Ca2+-dependent K+ channels. On the other hand, cinnarizine is a blocker of voltage-gated Ca2+ currents in hair cells and is used as a drug in conditions with vestibular vertigo. Our aim was to test in patch-clamp experiments (conventional whole-cell mode) whether cinnarizine, by reducing Ca2+ influx, inhibited Ca2+ and… 
Pharmacological modulation of transmitter release by inhibition of pressure-dependent potassium currents in vestibular hair cells
TLDR
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.
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  • T. Kimitsuki
  • Chemistry, Medicine
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  • 2013
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References

SHOWING 1-10 OF 33 REFERENCES
Inhibition of voltage-gated calcium currents in type II vestibular hair cells by cinnarizine
TLDR
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.
Potassium currents in type II vestibular hair cells isolated from the guinea-pig's crista ampullaris
TLDR
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.
Potassium depolarization of mammalian vestibular sensory cells increases [Ca2+]i through voltage‐sensitive calcium channels
TLDR
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.
Inward potassium rectifier current in type I vestibular hair cells isolated from guinea pig
TLDR
Large inward current activated by hyperpolarization was studied using whole cell patch clamp technique in type I vestibular hair cells of guinea pig and could contribute to restoration of the resting membrane potential during negative stimulations.
Potassium currents in vestibular type ii hair cells activated by hydrostatic pressure
TLDR
It is concluded that small elevations in hydrostatic pressure evoke a charybdotoxin-sensitive, probably Ca(2+)-dependent K(+) current in vestibular hair cells, which is likely to alter their frequency response and may be a relevant mechanism how hydro static pressure disturbs transduction.
Inactivating and non-inactivating delayed rectifier K+ currents in hair cells of frog crista ampullaris
TLDR
Current clamp experiments revealed that I(K,b), at variance with I (K,c), contributes to the cell resting potential and represents the main repolarizing current when sensory cells are depolarized from rest, which could have a role in hair cells when they are depolarsized after hyperpolarizing stimuli.
Voltage-gated calcium channel currents in type I and type II hair cells isolated from the rat crista.
TLDR
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 currents in auditory hair cells of the frog basilar papilla
TLDR
The kinetic properties of the ionic currents present in isolated BP hair cells argue against electrical tuning, a specialized spectral filtering mechanism reported in the hair cells of birds, reptiles, and amphibians, as a contributor to frequency selectivity of this organ.
Cav1.3 (α1D) Ca2+ Currents in Neonatal Outer Hair Cells of Mice
Outer hair cells (OHC) serve as electromechanical amplifiers that guarantee the unique sensitivity and frequency selectivity of the mammalian cochlea. It is unknown whether the afferent fibres
Calcium channels functional roles in the frog semicircular canal
TLDR
Results indicate that nimodipine-sensitive channels play a major role in afferent transmitter release, and ω-conotoxin GVIA sensitive channels regulate the afferent firing (possibly on the postsynaptic side) but with a less important role.
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