Meta-Biol

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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are nonselective ligand-gated cation channels in the plasma membranes of heart and brain cells. HCN channels are sometimes referred to as “pacemaker channels” because they help to generate rhythmic activity within groups of heart and brain cells. They are highly expressed in spontaneously active cardiac regions, such as the sinoatrial node (SAN, the natural pacemaker region), the atrioventricular node (AVN) and the Purkinje fibres of conduction tissue. HCN channels are encoded by four genes (HCN1, 2, 3, 4) and are widely expressed throughout the heart and the central nervous system. HCN channels are homotetramers of four subunits and conduct a Na+ and K+ current with a permeability of 1:4. The mixed sodium–potassium current activates upon hyperpolarization at voltages in the diastolic range (normally from −60/−70 mV to −40 mV). At the end of a sinoatrial action potential, the membrane repolarizes below −40/−50 mV, the "funny current" is activated and supplies inward current, which is responsible for starting the diastolic depolarization phase (DD); by this mechanism, the funny current controls the rate of spontaneous activity of sinoatrial myocytes, hence the cardiac rate. HCN channels are involved in controlling the rhythmic activity of pacemaker current in autorythymic cells in heart and neuronal processes such as dendritic integration and synaptic transmission.

Potassium channels are tetrameric ion channels that are widely distributed and are found in all cell types. Potassium channels control resting membrane potential in neurons, contribute to regulation of action potentials in cardiac muscle and help release of insulin form pancreatic beta cells.
Broadly K+ channels are classified into voltage gated K+ channels, Hyperpolarization activated cyclic nucleotide gated K+ channels (HCN), Tandem pore domain K+ channels, Ca2+ activated K+ channels and inwardly rectifying K+ channels.

The human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication among this astronomical number of elements. This communication occurs across synapses, the functional connection between neurons. Synapses can be divided into two general classes: electrical synapses and chemical synapses. Electrical synapses permit direct, passive flow of electrical current from one neuron to another. The current flows through gap junctions, specialized membrane channels that connect the two cells. Chemical synapses enable cell-to-cell communication using neurotransmitter release. Neurotransmitters are chemical agents released by presynaptic neurons that trigger a secondary current flow in postsynaptic neurons by activating specific receptor molecules. Neurotransmitter secretion is triggered by the influx of Ca2+ through voltage-gated channels, which gives rise to a transient increase in Ca2+ concentration within the presynaptic terminal. The rise in Ca2+ concentration causes synaptic vesicles (the presynaptic organelles that store neurotransmitters) to fuse with the presynaptic plasma membrane and release their contents into the space between the pre- and postsynaptic cells.