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- Title
The pharmacological action of Pimozide on vestibular Type-I and Type-II hair cells.
- Authors
Cheli, G.; Giunta, R.; Russo, G.; Masetto, S.
- Abstract
Pimozide is a conventional antipsychotic of the diphenylb-utylpiperidine class widely used for treating schizophrenia, delusional disorders, and managing motor and phonic tics in Tourette's syndrome. Its primary mechanism of action in the central nervous system is as a dopaminergic D2 receptor antagonist. Additionally, Pimozide is known for blocking various types of voltage-gated calcium and potassium channels. Among its side effects, dizziness and balance disorders are the most observed. This study delved into the effects of Pimozide on ionic currents in vestibular hair cells. Using the patch-clamp whole-cell technique, we studied the effect of Pimozide at a concentration of 3 μM on the ionic currents expressed by chicken embryo vestibular Type-I and Type-II hair cells, as well as on mammalian Type-II hair cells. Consistent with a previous report on chicken embryo, Pimozide significantly increased the delayed outward rectifying K+ current of Type-II hair cells on mouse. In chicken embryo, the drug also notably reduced the inward (anomalous) rectifying K+ current and the mixed Na+/K+ (Ih) current. In Type-I hair cells, Pimozide showed no significant effect on IK,L, a large low-voltage activated outward rectifying K+ current absent in Type-II cells, nor on the small delayed outward rectifying K+ current. The latter result suggests that the delayed rectifying K+ current involves different channel subunits in the two hair cell types. Additionally, Pimozide did not alter the inward Na+ current expressed by Type-I hair cells. In conclusion, these findings highlight that Pimozide selectively impacts potassium channels in Type-II, but not Type-I, hair cells. The drug acts as a delayed outward rectifying potassium channel opener in Type-II cells, potentially leading to a decrease in afferent signal transmission from these cells to primary sensory neurons. While providing a possible explanation for the vestibular side effects of Pimozide, the above results also open up possibilities for its use in reducing altered vestibular input in various vestibular disorders.
- Subjects
POLAND; HETEROCYCLIC compounds; POULTRY; CONFERENCES &; conventions; HAIR cells
- Publication
Journal of Hearing Science, 2024, Vol 14, Issue 3, p118
- ISSN
2083-389X
- Publication type
Article