Single I_h channels in pyramidal neuron dendrites: Properties, distribution, and impact on action potential output

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 single I_h channels in the apical dendrites of cortical layer 5 pyramidal neurons in vitro. In these neurons, we find that I_h channels have an average unitary conductance of 680 ± 30 fS (n = 18). Spectral analysis of simulated and native I_h channels showed that there is little or no channel flicker below 5 kHz. In contrast to the uniformly distributed single-channel conductance, I_h channel number increases exponentially with distance, reaching densities as high as ∼550 channels/μm² at distal dendritic sites. These high channel densities generate significant membrane voltage noise. By incorporating a stochastic model of I_h single-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 constant I_h current density. In addition, we demonstrate that voltage fluctuations attributable to stochastic I_h channel 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 of I_h is critical for maintaining the fidelity of action potential output.