Abolishing cAMP sensitivity in HCN2 pacemaker channels induces generalized seizures

Journal article

Publication Details

Author(s): Hammelmann V, Stieglitz MS, Huelle H, Le Meur K, Kass J, Bruemmer M, Gruner C, Roetzer RD, Fenske S, Hartmann J, Zott B, Luthi A, Spahn S, Moser M, Isbrandt D, Ludwig A, Konnerth A, Wahl-Schott C, Biel M
Journal: JCI Insight
Publication year: 2019
Volume: 4
Journal issue: 9
ISSN: 2379-3708


Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are dually gated channels that are operated by voltage and by neurotransmitters via the cAMP system. cAMP-dependent HCN regulation has been proposed to play a key role in regulating circuit behavior in the thalamus. By analyzing a knockin mouse model (HCN2EA), in which binding of cAMP to HCN2 was abolished by 2 amino acid exchanges (R591E, T592A), we found that cAMP gating of HCN2 is essential for regulating the transition between the burst and tonic modes of firing in thalamic dorsal-lateral geniculate (dLGN) and ventrobasal (VB) nuclei. HCN2EA mice display impaired visual learning, generalized seizures of thalamic origin, and altered NREM sleep properties. VB-specific deletion of HCN2, but not of HCN4, also induced these generalized seizures of the absence type, corroborating a key role of HCN2 in this particular nucleus for controlling consciousness. Together, our data define distinct pathological phenotypes resulting from the loss of cAMP-mediated gating of a neuronal HCN channel.

FAU Authors / FAU Editors

Ludwig, Andreas Prof. Dr.
Lehrstuhl für Pharmakologie und Toxikologie

External institutions
Ludwig-Maximilians-Universität (LMU)
Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry
Technische Universität München (TUM)
Universität Köln
Université de Lausanne (UNIL)

How to cite

Hammelmann, V., Stieglitz, M.S., Huelle, H., Le Meur, K., Kass, J., Bruemmer, M.,... Biel, M. (2019). Abolishing cAMP sensitivity in HCN2 pacemaker channels induces generalized seizures. JCI Insight, 4(9). https://dx.doi.org/10.1172/jci.insight.126418

Hammelmann, Verena, et al. "Abolishing cAMP sensitivity in HCN2 pacemaker channels induces generalized seizures." JCI Insight 4.9 (2019).


Last updated on 2019-23-05 at 00:08