Abstract
Lung diseases constitute a global health concern causing disability. According to WHO in 2016, respiratory diseases accounted for 24% of world population mortality, the second cause of death after cardiovascular diseases. The Kv7 channels family is a group of voltage-dependent K+ channels (Kv) encoded by KCNQ genes that are involved in various physiological functions in numerous cell types, especially, cardiac myocytes, smooth muscle cells, neurons, and epithelial cells. Kv7 channel α-subunits are regulated by KCNE1–5 ancillary β-subunits, which modulate several characteristics of Kv7 channels such as biophysical properties, cell-location, channel trafficking, and pharmacological sensitivity. Kv7 channels are mainly expressed in two large groups of lung tissues: pulmonary arteries (PAs) and bronchial tubes. In PA, Kv7 channels are expressed in pulmonary artery smooth muscle cells (PASMCs); while in the airway (trachea, bronchus, and bronchioles), Kv7 channels are expressed in airway smooth muscle cells (ASMCs), airway epithelial cells (AEPs), and vagal airway C-fibers (VACFs). The functional role of Kv7 channels may vary depending on the cell type. Several studies have demonstrated that the impairment of Kv7 channel has a strong impact on pulmonary physiology contributing to the pathophysiology of different respiratory diseases such as cystic fibrosis, asthma, chronic obstructive pulmonary disease, chronic coughing, lung cancer, and pulmonary hypertension. Kv7 channels are now recognized as playing relevant physiological roles in many tissues, which have encouraged the search for Kv7 channel modulators with potential therapeutic use in many diseases including those affecting the lung. Modulation of Kv7 channels has been proposed to provide beneficial effects in a number of lung conditions. Therefore, Kv7 channel openers/enhancers or drugs acting partly through these channels have been proposed as bronchodilators, expectorants, antitussives, chemotherapeutics and pulmonary vasodilators.
Highlights
Pulmonary Artery Smooth Muscle CellsThe expression of Kv7 channels in mice and rat pulmonary arteries (PAs) has been demonstrated in several studies
Specialty section: This article was submitted to Membrane Physiology and Membrane Biophysics, a section of the journal Frontiers in Physiology
In pulmonary arteries (PAs), Kv7 channels are expressed in pulmonary artery smooth muscle cells (PASMCs); while in the airway, Kv7 channels are expressed in airway smooth muscle cells (ASMCs), airway epithelial cells (AEPs), and vagal airway C-fibers (VACFs)
Summary
The expression of Kv7 channels in mice and rat PA has been demonstrated in several studies Complexes in vascular smooth muscle has been postulated on several studies (Chadha et al, 2014; Oliveras et al, 2014; Barrese et al, 2018). Kv7.4/7.5 heteromers have been proposed as the dominant functional vascular Kv7 channels, supported by electrophysiological data showing that Kv7 currents in freshly isolated vascular smooth muscle cells have phenotypes intermediate to the respective homomeric Kv7.4 and Kv7.5 channels (Brueggemann et al, 2014a; Chadha et al, 2014; Fosmo and Skraastad, 2017; Barrese et al, 2018). The main function of these channels is to regulate pulmonary vascular tone, due to their contribution to maintain the membrane potential (Em) of PASMC (Joshi et al, 2009; Sedivy et al, 2015; Mondejar-Parreño et al, 2018, 2019)
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