IHC analysis of HCN1 using SMC-304, tested on mouse cerebellum. Strong cytoplasm staining of the cerebellum giant neurons.

Ion channels are integral membrane proteins that help establish and control the small voltage gradient across the plasma membrane of living cells by allowing the flow of ions down their electrochemical gradient (1).  They are present in the membranes that surround all biological cells because their main function is to regulate the flow of ions across this membrane.  Whereas some ion channels permit the passage of ions based on charge, others conduct based on a ionic species, such as sodium or potassium.  Furthermore, in some ion channels, the passage is governed by a gate which is controlled by chemical or electrical signals, temperature, or mechanical forces.

There are a few main classifications of gated ion channels.  There are voltage- gated ion channels, ligand- gated, other gating systems and finally those that are classified differently, having more exotic characteristics.  The first are voltage- gated ion channels which open and close in response to membrane potential.  These are then separated into sodium, calcium, potassium, proton, transient receptor, and cyclic nucleotide-gated channels; each of which is responsible for a unique role.  Ligand-gated ion channels are also known as ionotropic receptors, and they open in response to specific ligand molecules binding to the extracellular domain of the receptor protein.  The other gated classifications include activation and inactivation by second messengers, inward-rectifier potassium channels, calcium-activated potassium channels, two-pore-domain potassium channels, light-gated channels, mechano-sensitive ion channels and cyclic nucleotide-gated channels.  Finally, the other classifications are based on less normal characteristics such as two-pore channels, and transient receptor potential channels (2).

Specifically, hyperpolarization-activated cation channels of the HCN gene family, such as HCN1, play a crucial role in the regulatons of cell excitability.  Importantly, they contribute to spontaneous rhythmic activity in both the heart and brain (3).

1. Hille B. (2001) Ion Channels of Excitable Membranes, 3rd Ed., Sinauer Associated Inc.:Sunderland, MA USA.
2. www.iochannels.org
3. Zong X., et al. (2005) J Biol Chem. 280(40): 34224-34232.