SingleIhChannels in Pyramidal Neuron Dendrites: Properties, Distribution, and Impact on Action Potential Output

Abstract

The hyperpolarization-activated cation current (I_h) plays an important role in regulating neuronal excitability, yet its native single-channel properties in the brain are essentially unknown. Here we use variance-mean analysis to study the properties of singleI_hchannels in the apical dendrites of cortical layer 5 pyramidal neuronsin vitro. In these neurons, we find thatI_hchannels have an average unitary conductance of 680 ± 30 fS (n= 18). Spectral analysis of simulated and nativeI_hchannels showed that there is little or no channel flicker below 5 kHz. In contrast to the uniformly distributed single-channel conductance,I_hchannel number increases exponentially with distance, reaching densities as high as ∼550 channels/μm²at distal dendritic sites. These high channel densities generate significant membrane voltage noise. By incorporating a stochastic model ofI_hsingle-channel gating into a morphologically realistic model of a layer 5 neuron, we show that this channel noise is higher in distal dendritic compartments and increased threefold with a 10-fold increased single-channel conductance (6.8 pS) but constantI_hcurrent density. In addition, we demonstrate that voltage fluctuations attributable to stochasticI_hchannel gating impact on action potential output, with greater spike-timing precision in models with the experimentally determined single-channel conductance. These data suggest that, in the face of high current densities, the small single-channel conductance ofI_his critical for maintaining the fidelity of action potential output.