Regulation of recombinant and native hyperpolarization-activated cation channels.
Ionic currents generated by hyperpolarization-activated cation-nonselective (HCN) channels have been principally known as pacemaker h-currents (Ih), because they allow cardiac and neuronal cells to be rhythmically active over precise intervals of time. Presently, these currents are implicated in numerous additional cellular functions, including neuronal integration, synaptic transmission, and sensory reception. These roles are accomplished by virtue of the regulation of Ih by both voltage and ligands. The article summarizes recent developments on the properties and allosteric interactions of these two regulatory pathways in cloned and native channels. Additionally, it discusses how the expression and properties of native channels may be controlled via regulation of the transcription of the HCN channel gene family and the assembly of channel subunits. Recently, several cardiac and neurological diseases were found to be intimately associated with a dysregulation of HCN gene transcription, suggesting that HCN-mediated currents may be involved in the pathophysiology of excitable systems. As a starting point, we briefly review the general characteristics of Ih and the regulatory mechanisms identified in heterologously expressed HCN channels.
Frère
Samuel G A
SG
Section of Pharmacology and Neurobiology, Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
Kuisle
Mira
M
Lüthi
Anita
A
D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D015221:Potassium Channels; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D011994:Recombinant Proteins