Abstract
We have previously reported in a feline model of acute peripheral vestibulopathy (APV) that the sudden, unilateral, and irreversible loss of vestibular inputs induces selective overexpression of small conductance calcium-activated potassium (SK) channels in the brain stem vestibular nuclei. Pharmacological blockade of these ion channels by the selective antagonist apamin significantly alleviated the evoked vestibular syndrome and accelerated vestibular compensation. In this follow-up study, we aimed at testing, using a behavioral approach, whether the antivertigo (AV) effect resulting from the antagonization of SK channels was species-dependent or whether it could be reproduced in a rodent APV model, whether other SK channel antagonists reproduced similar functional effects on the vestibular syndrome expression, and whether administration of SK agonist could also alter the vestibular syndrome. We also compared the AV effects of apamin and acetyl-DL-leucine, a reference AV compound used in human clinic. We demonstrate that the AV effect of apamin is also found in a rodent model of APV. Other SK antagonists also produce a trend of AV effect when administrated during the acute phase of the vertigo syndrome. Conversely, the vertigo syndrome is worsened upon administration of SK channel agonist. It is noteworthy that the AV effect of apamin is superior to that of acetyl-DL-leucine. Taken together, these data reinforce SK channels as a pharmacological target for modulating the manifestation of the vertigo syndrome during APV.
Highlights
We demonstrated in a unilateral vestibular neurectomy (UVN) cat model, that administration of apamin during the acute phase of the vestibular syndrome significantly reduced both the posturo-locomotor and vestibulo-ocular deficits
To study more thoroughly the antivertigo effect of apamin, we investigated in this follow-up study whether this effect could be reproduced in a rodent model of acute peripheral vestibulopathy, by other SK channel antagonists, and whether SK channel agonists may produce a comparable or opposite antivertigo effect
In the Results section, data are presented as statistical value, degrees of freedom, and exact p value. These data confirm the significant antivertigo benefit of apamin in vestibuloinjured rats, with improvement of locomotion and mobility shortly after the insult, and reduction of syndrome intensity and improvement of both velocity and distance traveled after a week
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Apamin is a globular peptide neurotoxin of 18 amino acids present in the apitoxin-bee venom [1]. It is a polypeptide with the following amino acid sequence: H-Cys-Asn-CysLys-Ala-Pro-Glu-Thr-Ala-Leu-Cys-Ala-Arg-Arg-Cys-Gln-Gln-His-NH2. The two disulfuric bridges between Cys1-Cys and Cys3-Cys together with the seven hydrogen bonds make apamin a highly stable molecule. Dry bee venom is composed of 2–3% apamin [2]
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