Review Article

The Role of HCN Channels on Membrane Excitability in the Nervous System

Figure 5

The roles of HCN channels are influenced by K+ channel and Ca2+ channel, and also modulated by voltage dependence. Values of channel conductance density (S/cm2) are shown in insets. (a) Typical EPSP traces in models with different HCN and muscarinic K+ (Km) channel conductances. Synaptic input of the same intensity is applied in the soma in this simulation. The initial membrane potential is not modified by current injection. (b) The relationship between membrane potential at the peak of EPSP ( 𝑉 p e a k ) and intensity of synaptic input in models with different HCN and Km channel conductances. The 𝑉 p e a k -intensity curves with and without HCN channel conductance cross. The cross points shift in a Km channel conductance-dependent manner. (c) Relation between 𝑉 p e a k and intensity of synaptic input in models with different HCN and Km channel conductances. Open diamonds indicate the threshold intensities for spike generation. The effect of adding HCN channel conductance is shown by arrows. Direction of the arrows is dependent on Km channel conductance. (d) Relationship between the minimum intensity of synaptic input to generate action potential and Km channel conductance in models with (open circles) and without (filled circles) HCN channels. When the Km channel conductance is small, the minimum intensity is smaller in the model with HCN channels than the model without HCN channels. In such a range of Km channel conductance, the role of HCN channels is excitatory. In contrast, when Km channel conductance is large, the main role of HCN channels is inhibitory. (e) Relation between 𝑉 p e a k and intensity of synaptic input in models with different HCN and CaV3 channel conductances. CaV3 conductance shifts the relation to the excitatory direction (to the left), whereas Km channel conductance shifts it to the inhibitory direction (to the right). (c) The influence of CaV3 channel conductance appears milder than that of Km channel conductance. The effect of adding HCN channel conductance is shown by arrows. Direction of the arrows is independent of CaV3 conductance. (f) Relationship between the minimum intensity of synaptic input to generate action potential and CaV3 channel conductance in models with different HCN channel conductance. HCN channel conductance always functions as an inhibitory factor for action potential generation in out simulation, because condition with lower HCN channel density resulted in lower minimum stimulus intensity in all CaV3 conductance. (g) Relationship between 𝑉 p e a k and intensity of synaptic input in models with different HCN channel conductance and voltage dependence. Open diamonds indicate the threshold intensities of synaptic input to generate action potential. Hyperpolarization and depolarization of voltage dependence, respectively, shift the relation to excitatory and inhibitory directions. These effects are similar to the modulation of HCN channel conductance. (h) Minimum intensity of synaptic input to generate action potential in models with different voltage dependencies of HCN channels.
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