European Journal of Neuroscience 2012-12-01

Differential effects of blockade of ERG channels on gamma oscillations and excitability in rat hippocampal slices.

Silvia Fano, Gürsel Çalışkan, Uwe Heinemann

Index: Eur. J. Neurosci. 36(12) , 3628-35, (2012)

Full Text: HTML

Abstract

Agents such as sertindole and astemizole affect heart action by inducing long-QT syndrome, suggesting that apart from their neuronal actions through histamine receptors, 5-HT2 serotonin receptors and D2 dopamine receptors they also affect ether-a-go-go channels and particularly ether-a-go-go-related (ERG) potassium (K(+)) channels, comprising the K(v) 11.1, K(v) 11.2 and K(v) 11.3 voltage-gated potassium currents. Changes in ERG K(+) channel expression and activity have been reported and may be linked to schizophrenia [Huffaker, S.J., Chen, J., Nicodemus, K.K., Sambataro, F., Yang, F., Mattay, V., Lipska, B.K., Hyde, T.M., Song, J., Rujescu, D., Giegling, I., Mayilyan, K., Proust, M.J., Soghoyan, A., Caforio, G., Callicott, J.H., Bertolino, A., Meyer-Lindenberg, A., Chang, J., Ji, Y., Egan, M.F., Goldberg, T.E., Kleinman, J.E., Lu, B. & Weinberger DR. (2009). Nat. Med., 15, 509-518; Shepard, P.D., Canavier, C.C. & Levitan, E.S. (2007). Schizophr Bull., 33, 1263-1269]. We have previously shown that histamine H1 blockers augment gamma oscillations (γ) which are thought to be involved in cognition and storage of information. These effects were particularly pronounced for γ induced by acetylcholine. Here we have compared neuronal effects of three agents which interfere with ERG K(+) channels. We found that astemizole and sertindole, but not the K(v) 11 channel blocker E4031, augmented γ induced by acetylcholine in hippocampal slices. Kainate-induced γ were only affected by astemizole. Evoked responses induced by stratum radiatum stimulation in area CA1 revealed that only E4031 augmented stimulus-induced synaptic potentials and neuronal excitability. Our findings suggest that K(v) 11 channels are involved in neuronal excitability without clear effects on γ and that the effect of astemizole is related to actions on H1 receptors.© 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.


Related Compounds

Related Articles:

Antihistamines modulate the integrin signaling pathway in h9c2 rat cardiomyocytes: Possible association with cardiotoxicity.

2015-08-01

[Hum. Exp. Toxicol. 34 , 796-807, (2015)]

Tuning of EAG K(+) channel inactivation: molecular determinants of amplification by mutations and a small molecule.

2012-09-01

[J. Gen. Physiol. 140(3) , 307-24, (2012)]

Astemizole: a long-acting, nonsedating antihistamine.

1987-12-01

[Drug Intell. Clin. Pharm. 21(12) , 947-53, (1987)]

[Astemizole: its pharmacokinetics and pharmacologic properties].

1990-06-01

[Allerg. Immunol. (Paris.) 22(6) , 233-41, (1990)]

The possible involvement of hyperpolarizing mechanisms in histamine-induced relaxation of the rat portal vein.

2008-01-01

[J. Smooth Muscle Res. 44(3-4) , 129-41, (2008)]

More Articles...