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

Daisuke Kase,Keiji Imoto

doi:10.1155/2012/619747

Abstract

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels were first reported in heart cells and are recently known to be involved in a variety of neural functions in healthy and diseased brains. HCN channels generate inward currents when the membrane potential is hyperpolarized. Voltage dependence of HCN channels is regulated by intracellular signaling cascades, which contain cyclic AMP, PIP2, and TRIP8b. In addition, voltage-gated potassium channels have a strong influence on HCN channel activity. Because of these funny features, HCN channel currents, previously called funny currents, can have a wide range of functions that are determined by a delicate balance of modulatory factors. These multifaceted features also make it difficult to predict and elucidate the functional role of HCN channels in actual neurons. In this paper, we focus on the impacts of HCN channels on neural activity. The functions of HCN channels reported previously will be summarized, and their mechanisms will be explained by using numerical simulation of simplified model neurons.

Highlights

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, first identified in 1976 in the heart by Noma and Irisawa [1] and characterized by Brown and Difrancesco [2] and Weiss and his colleague [3], are cation channels that open when the membrane potential is hyperpolarized
Cyclic-AMP-(cAMP-) binding site locates near the C terminus, and cAMP affects the voltage dependence of activation in some HCN channel isoforms [10]
This paper focuses on the electrophysiological function of HCN channels in the central nervous system

Summary

Introduction

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, first identified in 1976 in the heart by Noma and Irisawa [1] and characterized by Brown and Difrancesco [2] and Weiss and his colleague [3], are cation channels that open when the membrane potential is hyperpolarized. Cyclic-AMP-(cAMP-) binding site locates near the C terminus, and cAMP affects the voltage dependence of activation in some HCN channel isoforms [10]. Phosphatidylinositol 4,5-bisphosphate (PIP2) is known as a modulator of HCN channels; it shifts the voltage dependence through a different mechanism from that of cAMP [11, 12]. These multifaceted features endow HCN channels to work in many functions described below. We try to understand the physiological significance of these functions by using simple numerical simulations

Expression Pattern

Functional Roles of HCN Channels

Influence of Other Ion Channels on the Roles of HCN Channels

Effects of Modulators of HCN Channel

Involvement of HCN Channels in Neural Diseases

Conclusion

Simulation Condition