HCN channels conduct the hyperpolarization-activated cation current Ih which contributes to neuronal pacemaking, controls the resting membrane potential, and modulates synaptic transmission and integration. Ih current density has been found to be regulated during development and by both physiologic and abnormal patterns of neuronal activity. Drebrin A is a neuron-specific F- actin binding protein found exclusively in postsynaptic compartments of excitatory synapses. It has been implicated in developmental spine morphogenesis and activity-dependent synaptic targeting of NMDA receptors. Here we demonstrate that expression of Drebrin A increases HCN2 channel surface expression. Pulse-chase experiments with extracellularly labeled HCN2 suggest that the increase in channel surface expression is due to a decrease in its internalization rate. As the effect is not observed upon coexpression with mutant Drebrin A lacking its actin binding domain, we hypothesize that actin remodeling by Drebrin A underlies the increase in HCN2 surface expression. To test this hypothesis, we are currently investigating the influence of drugs polymerizing or depolymerizing actin filaments on Drebrin A mediated changes in HCN2 surface expression.

(supported by the DFG: GRK843 and KL1168/6).