Other ion channels

Other ion channel families include the aquaporins (which also includes aquaglyceroporins), a family of chloride channels which includes the cystic fibrosis transmembrane conductance regulator (CFTR), the connexins and pannexins and the sodium leak channel, non-selective.

Genetic defects in aquaporin genes have been associated with several human diseases including abnormalities of renal water regulation, nephrogenic diabetes insipidus, loss of vision, onset of brain edema and starvation. Agre and Kozono (2003) and Schrier (2007) discuss the role of aquaporins in human health and disease.

The CFTR potentiator drug ivacaftor and the CFTR correcting drug lumacaftor are approved to treat a subset of cystic fibrosis patients. Crofelemer, a medication used to treat HIV-AIDS related diarrhea, is a CFTR activator. It also activates another unrelated chloride channel, CaCC, a calcium-activated chloride channel.

The connexin and pannexin genes encode gap junction proteins in humans, Gap junctions are essential for many physiological processes including cardiac and smooth muscle contraction, regulation of neuronal excitability and epithelial electrolyte transport. Connexins and pannexins allow the passive diffusion of molecules of up to 1,000 Daltons which can include nutrients, metabolites and second messengers (such as IP₃) as well as cations and anions. Mutations in connexin genes are associated with the occurrence of a number of pathologies, such as peripheral neuropathies, cardiovascular diseases and hereditary deafness.

The sodium leak channel, non-selective (provisionally assigned as Na_Vi2.1) is structurally related to the voltage-gated sodium channel family (Na_v1.1 – Na_v1.9), but is voltage-insensitive and displays distinctive ion selectivity and pharmacological properties. Na_Vi2.1 is is widely distributed within the central nervous system and is also expressed in the heart and pancreas, and may mediate the tetrodotoxin-resistant and voltage-insensitive Na⁺ leak current (I_L-Na) observed in many types of neuron (see Lu et al. (2007) for further details). The calcium channel blocker verapamil also blocks Na_Vi2.1.