title: Voltage-dependent BK and Hv1 channels expressed in non-excitable tissues: New therapeutics opportunities as targets in human diseases.
abstract: Voltage-gated ion channels are the molecular determinants of cellular excitability. This group of ion channels is one of the most important pharmacological targets in excitable tissues such as nervous system, cardiac and skeletal muscle. Moreover, voltage-gated ion channels are expressed in non-excitable cells, where they mediate key cellular functions through intracellular biochemical mechanisms rather than rapid electrical signaling. This review aims at illustrating the pharmacological impact of these ion channels, highlighting in particular the structural details and physiological functions of two of them - the high conductance voltage- and Ca(2+)-gated K(+) (BK) channels and voltage-gated proton (Hv1) channels- in non-excitable cells. BK channels have been implicated in a variety of physiological processes ranging from regulation of smooth muscle tone to modulation of hormone and neurotransmitter release. Interestingly, BK channels are also involved in modulating K(+) transport in the mammalian kidney and colon epithelium with a potential role in the hyperkalemic phenotype observed in patients with familial hyperkalemic hypertension type 2, and in the pathophysiology of hypertension. In addition, BK channels are responsible for resting and stimulated Ca(2+)-activated K(+) secretion in the distal colon. Hv1 channels have been detected in many cell types, including macrophages, blood cells, lung epithelia, skeletal muscle and microglia. These channels have a central role in the phagocytic system. In macrophages, Hv1 channels participate in the generation of reactive oxygen species in the respiratory burst during the process of phagocytosis.
authors: Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile. Electronic address: fjmorera@uach.cl.
authors: Francisco J
authors: FJ
authors: Morera
authors: Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile.
authors: Julia
authors: J
authors: Saravia
authors: Institute of Marine Sciences and Limnology, Faculty of Sciences, Universidad Austral de Chile, Valdivia, Chile.
authors: Juan Pablo
authors: JP
authors: Pontigo
authors: Institute of Marine Sciences and Limnology, Faculty of Sciences, Universidad Austral de Chile, Valdivia, Chile.
authors: Luis
authors: L
authors: Vargas-Chacoff
authors: Interdisciplinary Center for Neuroscience of Valparaiso, Faculty of Sciences, Universidad de Valparaiso, Valparaiso, Chile.
authors: Gustavo F
authors: GF
authors: Contreras
authors: Interdisciplinary Center for Neuroscience of Valparaiso, Faculty of Sciences, Universidad de Valparaiso, Valparaiso, Chile.
authors: Amaury
authors: A
authors: Pupo
authors: Interdisciplinary Center for Neuroscience of Valparaiso, Faculty of Sciences, Universidad de Valparaiso, Valparaiso, Chile.
authors: Yenisleidy
authors: Y
authors: Lorenzo
authors: Interdisciplinary Center for Neuroscience of Valparaiso, Faculty of Sciences, Universidad de Valparaiso, Valparaiso, Chile.
authors: Karen
authors: K
authors: Castillo
authors: Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubcock, TX, USA.
authors: Cholpon
authors: C
authors: Tilegenova
authors: Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubcock, TX, USA. Electronic address: luis.cuello@ttuhsc.edu.
authors: Luis G
authors: LG
authors: Cuello
authors: Interdisciplinary Center for Neuroscience of Valparaiso, Faculty of Sciences, Universidad de Valparaiso, Valparaiso, Chile. Electronic address: carlos.gonzalezl@uv.cl.
authors: Carlos
authors: C
authors: Gonzalez
mesh_terms: D004358:Drug Therapy; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D008958:Models, Molecular; D058990:Molecular Targeted Therapy
chemical_list: C510235:HVCN1 protein, human; D007473:Ion Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels
keywords: BK channel; H(v)1 channel; Phagocytosis; Potassium secretion; Voltage-dependent potassium channels; Voltage-dependent proton channel