Purkinje cell hyperexcitability and depressive-like behavior in mice lacking erg3 (ether-à-go-go-related gene) K⁺ channel subunits.

Abstract

Potassium channels stabilize the resting potential and neuronal excitability. Among them, erg (ether-à-go-go-related gene) K⁺ channels represent a subfamily of voltage-gated channels, consisting of erg1, erg2, and erg3 subunits; however, their subunit-specific neuronal functions in vivo are barely understood. To find erg3- and erg1-mediated functions, we generated global <i>Kcnh7</i> (<i>erg3</i>) and conditional <i>Kcnh2</i> (<i>erg1</i>) knockout mice. We found that erg3 channels stabilize the resting potential and dampen spontaneous activity in cerebellar Purkinje cells (PCs) and hippocampal CA1 neurons, whereas erg1 channels have suprathreshold functions. Lack of erg3 subunits induced hyperexcitability with increased action potential firing in PCs, but not in CA1 neurons. Notably, erg3 depletion caused depressive-like behavior with reduced locomotor activity, strongly decreased digging behavior, and shorter latencies to fall off a rotating wheel, while learning and memory remained unchanged. Our data show that erg K⁺ channels containing erg3 subunits mediate a neuronal subthreshold K⁺ current that plays important roles in the regulation of locomotor behavior in vivo.