Dysfunctional Hyper Polarization Activated Cyclic Nucleotide-Gated Ion Channels in Cardiac Diseases

Tianxiang Gu,Xiaoqi Zhao

doi:10.5935/1678-9741.20160030

Abstract

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are reverse voltage-dependent, and their activation depends on the hyperpolarization of the membrane and may be directly or indirectly regulated by the cyclic adenosine monophosphate (cAMP) or other signal-transduction cascades. The distribution, quantity and activation states of HCN channels differ in tissues throughout the body. Evidence exhibits that HCN channels play critical roles in the generation and conduction of the electrical impulse and the physiopathological process of some cardiac diseases. They may constitute promising drug targets in the treatment of these cardiac diseases. Pharmacological treatment targeting HCN channels is of benefit to these cardiac conditions.

Highlights

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a family of cation channels activated by hyperpolarized membrane potentials and stimulated by intracellular cyclic nucleotides
The expression of HCN channel is age-related, the expression has difference in distinct growth stages, HCN genes are inactivated in ventricular myocytes cells following maturation whereas they expressed in these cells in the fetal and/or neonatal heart[5,6,7,8]
In the healthy adult heart, HCN channels are predominantly expressed in the conduction system, especially in the sinoatrial node, HCN4 has been determined as the principal HCN isoform in sinoatrial node cells

Summary

INTRODUCTION

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a family of cation channels activated by hyperpolarized membrane potentials and stimulated by intracellular cyclic nucleotides. In the healthy adult heart, HCN channels are predominantly expressed in the conduction system, especially in the sinoatrial node, HCN4 has been determined as the principal HCN isoform in sinoatrial node cells. HCN2 has long been known to be expressed in cardiac ventricular myocytes[10], and recently, the expression of HCN4 and low amounts of HCN1 and in addition a functional role of HCN3 in ventricular myocytes has been demonstrated[11,12], but the expression of HCN channels in healthy adult ventricular myocardium is generally weaker than in the conduction system, so If currents are rarely detectable in normal ventricular myocytes[13,14]. Positive inotropic effect of thyroid hormone may be associated with upregulation of the channel molecules[16,17]

HCN AND CARDIOMYOPATHY

Letter to the Editor

HCN AND ARRHYTHMIAS

Findings

HCN CHANNEL BLOCKERS