Single Ih channels in pyramidal neuron dendrites: properties, distribution, and impact on action potential output.
The hyperpolarization-activated cation current (Ih) 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 Ih channels in the apical dendrites of cortical layer 5 pyramidal neurons in vitro. In these neurons, we find that Ih channels have an average unitary conductance of 680 +/- 30 fS (n = 18). Spectral analysis of simulated and native Ih channels showed that there is little or no channel flicker below 5 kHz. In contrast to the uniformly distributed single-channel conductance, Ih channel number increases exponentially with distance, reaching densities as high as approximately 550 channels/microm2 at distal dendritic sites. These high channel densities generate significant membrane voltage noise. By incorporating a stochastic model of Ih 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 Ih current density. In addition, we demonstrate that voltage fluctuations attributable to stochastic Ih 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 Ih is critical for maintaining the fidelity of action potential output.
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra 0200, Australian Capital Territory, Australia. maarten.kole@anu.edu.au
Maarten H P
MH
Kole
Stefan
S
Hallermann
Greg J
GJ
Stuart
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D003712:Dendrites / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
D007473:Ion Channels