Ionic Basis for Membrane Potential Resonance in Neurons of the Inferior Olive

Abstract

Some neurons have the ability to enhance output voltage to input current with a preferred frequency, which is called resonance. Resonance is thought tobe a basis for membrane potential oscillation. Although ion channels responsible for resonance have been reported, the precise mechanisms by which these channels work remain poorly understood. We have found that resonance is reduced but clearly present in the inferior olivary neurons ofCav3.1 T-type voltage-dependent Ca(2+) channel knockout (KO) mice. The activation of Cav3.1 channels is strongly membrane potential dependent, but less frequency dependent. Residual resonance in Cav3.1 KO mice is abolished by a hyper-polarization-activated cyclic nucleotide-gated (HCN) channelblocker, ZD7288, and is partially suppressed byvoltage-dependent K(+) channel blockers. Resonance is inhibited by ZD7288 in wild-type mice andimpaired in HCN1 KO mice, suggesting that theHCN1 channel is essentialfor resonance. The ZD7288-sensitive current is nearly sinusoidal and strongly frequency dependent. These results suggest that Cav3.1 and HCN1 channels act as amplifying and resonating conductances, respectively.