Cyclic nucleotide-gated (HCN) channels that are activated by hyperpolarization are vital messengers within cells, especially in the nervous system where they are crucial in controlling neuronal excitability. These channels have a role in producing rhythmic activity, including heart and brain pacemaker currents. They are of great interest in neurology and medicine due to their special qualities. Although HCN channels are present in many bodily tissues, research on them has focused primarily on the heart and brain. They are in charge of the hyperpolarization-activated current (I_h) in neurons. HCN channels serve a critical role in regulating the rate of neuronal activity since this current is essential for establishing the resting membrane potential and the frequency of action potential firing. HCN channels are tetramers structurally, consisting of four distinct subunits. Six transmembrane domains (S1–S6) make up each subunit, and the voltage sensor is located in the S4 segment. The distinct gating mechanism of HCN channels, which combines voltage and cyclic nucleotides, sets them apart from other potassium channels. One characteristic that sets HCN channels apart is their cyclic nucleotide-binding domain (CNBD), which enables them to react to intracellular cyclic nucleotides such as cAMP (cyclic adenosine monophosphate) and cGMP (cyclic guanosine monophosphate). Cyclic nucleotides boost channel opening by binding to the CNBD, which increases the inward current that potassium and sodium ions carry. The heart's sinoatrial node cells and some brain neurons exhibit pacemaker activity, which is attributed to a process called hyperpolarization-activated current. The production of the funny current (I_f), which aids in determining heart rate, depends critically on HCN channels in the heart. By modifying the odd current, drugs that target HCN channels have been produced to treat ailments including cardiac arrhythmias. HCN channels are present in the brain regions related to memory, learning, and rhythmic activity. Processes including synaptic integration, dendritic excitability, and theta rhythm production depend on their function in these areas. All things considered, HCN channels are intriguing molecules that connect the domains of chemical regulation and electrical communication, making them attractive candidates for therapeutic treatments in illnesses ranging from neurological diseases to cardiac arrhythmias.
