Cyclic nucleotide regulated channels

The family of cyclic nucleotide-regulated channels comprises two structurally related groups: CNG and HCN channels. Cyclic nucleotide-gated channels (CNG) are ligand-gated channels that are activated upon binding of cAMP or cGMP. Hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are principally activated by membrane hyperpolarization. Cyclic nucleotides facilitate activation of these channels.

CNG channels are essential for visual and olfactory transduction and are also involved in other processes of the nervous system. Our laboratory is interested in the function and in vivo regulation of CNG channel complexes. In particular, we examine the pathomechanism of blinding diseases associated with CNG channel dysfunction (e.g. retinitis pigmentosa, achromatopsia). Based on these studies, we develop advanced gene therapy approaches to rescue vision.

HCN channels play a key role in controling cardiac rhythmicity (“pacemaker” channels) and are crucial determinants of neuronal excitability. Since our discovery of HCN channels in the late nineties, we have extensively studied the function and regulation of these channels. We are seeking to dissect the specific roles of individual HCN channel types in heart and in complex neuronal circuits under physiological and pathophysiological conditions.

Generalized seizures in a genetic knock-in mouse           Expression of the HCN4 channel in sinoatrial

model expressing a cAMP-deficient HCN2 channel           pacemaker cells

Further reading

Hennis et al. (2022) Nat Protoc

Hennis et al. (2021) Front Physiol

Fenske et al. (2020) Nat Commun

Hammelmann et al. (2019) JCI Insight

Biel et al. (2009) Physiol Rev