The hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channel gene family is known to contribute significantly to cardiac pacemaking via pacemaker currents. To date, there are four mammalian HCN isoforms (HCN1–4) identified. The importance of HCN channel function to normal cardiac automaticity in mice was recently corroborated in humans diagnosed with idiopathic sinus node dysfunct...

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are subthreshold activated voltage-gated ion channels. In the cortex, these channels are predominantly expressed in dendrites where they significantly modify dendritic intrinsic excitability as well synaptic potential shapes and integration. HCN channel trafficking to dendrites is regulated by the protein, TRIP8b. Additionally, ...

Theoretical and computational frameworks for synaptic plasticity and learning have a long and cherished history, with few parallels within the well-established literature for plasticity of voltage-gated ion channels. In this study, we derive rules for plasticity in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, and assess the synergy between synaptic and HCN channel pla...

cAMP signaling in the brain mediates several higher order neural processes. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels directly bind cAMP through their cytoplasmic cyclic nucleotide binding domain (CNBD), thus playing a unique role in brain function. Neuronal HCN channels are also regulated by tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), an aux...

The onset of spontaneous seizures in the pilocarpine model of epilepsy causes a hyperpolarized shift in the voltage-dependent activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated current (Ih) in CA1 hippocampal pyramidal neuron dendrites, contributing to neuronal hyperexcitability and possibly to epileptogenesis. However, the specific mechanisms by which spon...

BACKGROUND The pacemaker current I(f) is present in atrial and ventricular myocytes. However, it remains controversial whether I(f) overexpression in diseased states might play a role for arrhythmogenesis, because first I(f) activation in whole-cell recordings hardly overlapped the diastolic voltage of working myocardium. METHODS AND RESULTS To obtain further insight into I(HCN) and I(f) prop...

Hyperpolarization-activated, cyclic nucleotide-gated, nonspecific cation (HCN) channels have a well-characterized role in regulation of cellular excitability and network activity. The role of these channels in control of epileptiform discharges is less thoroughly understood. This is especially pertinent given the altered HCN channel expression in epilepsy. We hypothesized that inhibition of HCN...

Background—The pacemaker current If is present in atrial and ventricular myocytes. However, it remains controversial whether If overexpression in diseased states might play a role for arrhythmogenesis, because first If activation in whole-cell recordings hardly overlapped the diastolic voltage of working myocardium. Methods and Results—To obtain further insight into IHCN and If properties, we p...

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels were first reported in heart cells and are recently known to be involved in a variety of neural functions in healthy and diseased brains. HCN channels generate inward currents when the membrane potential is hyperpolarized. Voltage dependence of HCN channels is regulated by intracellular signaling cascades, which contain cycl...

Hyperpolarization-activated cation (HCN) channels give rise to an inward current with similar but not identical characteristics compared with the pacemaker current (I(f)), suggesting that HCN channel function is modulated by regulatory beta-subunits in native tissue. KCNE2 has been proposed to serve as a beta-subunit of HCN channels; however, available data remain contradictory. To further clar...