Abstract
Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the “funny” pacemaker current (If), a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.
Highlights
The cardiac impulse originates in the sinus atrial node (SAN), located at the right atrial endocardium, between the upper and lower cava vein, and formed by highly specialized cells able to generate action potentials (APs) which start sinus rhythm.These action potentials are fundamental in order to allow cardiac muscle cells to contract and make the heart to play its work
The K+ efflux tends to re-polarize the cell after the ascending phase of the action potential and it continues far beyond the maximum period of repolarization, a reduction in amplitude is observed during phase 4 of the AP period
Molecular approaches have tried to clarify the relationships between mutations of the Hyperpolarization and Cyclic Nucleotide (HCN) channels genes and alterations in the cardiac function, above all according to a simple arrhythmic level
Summary
The cardiac impulse originates in the sinus atrial node (SAN), located at the right atrial endocardium, between the upper and lower cava vein, and formed by highly specialized cells able to generate action potentials (APs) which start sinus rhythm. These action potentials are fundamental in order to allow cardiac muscle cells to contract and make the heart to play its work. There are many currents (both inward and outward) involved in the functioning of the SAN, able to determine the profile of the final current. If, induced by hyperpolarization; An inward current of calcium, ICa; An outward current, Ik
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