Abstract
Large-conductance Ca2+-activated K+ channels facilitate the efflux of K+ ions from a variety of cells and tissues following channel activation. It is now recognized that BK channels undergo a wide range of pre- and post-translational modifications that can dramatically alter their properties and function. This has downstream consequences in affecting cell and tissue excitability, and therefore, function. While finding the “silver bullet” in terms of clinical therapy has remained elusive, ongoing research is providing an impressive range of viable candidate proteins and mechanisms that associate with and modulate BK channel activity, respectively. Here, we provide the hallmarks of BK channel structure and function generally, and discuss important milestones in the efforts to further elucidate the diverse properties of BK channels in its many forms.
Highlights
INTRODUCTIONLarge-conductance Ca2+-activated K+ or BK [Big Potassium (K+)] channels, known as Maxi-K, Slo or KCa1.1 channels, are ubiquitously expressed in a broad array of excitable and non-excitable cells including neurons/glial cells (Trimmer, 2015; Hayashi et al, 2016; Latorre et al, 2017), a variety of vascular or nonvascular smooth muscle (Nelson et al, 1995; Nelson and Quayle, 1995; Brenner et al, 2005; Herrera et al, 2005; Hu and Zhang, 2012; Kyle et al, 2013; Krishnamoorthy-Natarajan and Koide, 2016; Dopico et al, 2018), skeletal muscle (Pallotta et al, 1981), neuroendocrine cells (Solaro et al, 1995) and, epithelial cells (Manzanares et al, 2011; Yang et al, 2017)
We provide an overview of the basic biophysical features, including structural, functional and pharmacological properties of mammalian BK channels, with a particular focus on their pathological implication as well as their potential as molecular targets for the development of innovative and promising therapeutic strategies in the nervous and cardiovascular systems
BK channel activity may be regulated via a wide variety of intracellular signaling molecules that bind to the cytoplasmic domain of the channel, including Mg2+, which depending on its concentration, can exert opposing effects in the activity of BK channels
Summary
Large-conductance Ca2+-activated K+ or BK [Big Potassium (K+)] channels, known as Maxi-K, Slo or KCa1.1 channels, are ubiquitously expressed in a broad array of excitable and non-excitable cells including neurons/glial cells (Trimmer, 2015; Hayashi et al, 2016; Latorre et al, 2017), a variety of vascular or nonvascular smooth muscle (Nelson et al, 1995; Nelson and Quayle, 1995; Brenner et al, 2005; Herrera et al, 2005; Hu and Zhang, 2012; Kyle et al, 2013; Krishnamoorthy-Natarajan and Koide, 2016; Dopico et al, 2018), skeletal muscle (Pallotta et al, 1981), neuroendocrine cells (Solaro et al, 1995) and, epithelial cells (Manzanares et al, 2011; Yang et al, 2017) These channels are characterized by exhibiting a high K+ selectivity, a large single channel conductance of 200–300 pS (~10–20-fold greater that other K+ channels), and an exquisite ability to be dually activated by two distinct physiological stimuli: membrane depolarization and local increases in intracellular Ca2+ (Marty, 1981; Pallotta et al, 1981; Barrett et al, 1982; Latorre et al, 1982, 1989; Marty, 1989). The structural features of the α-subunit confer unique biophysical properties to the channel including ion permeation, BIOPHYSICAL FEATURES OF LARGECONDUCTANCE Ca2+-ACTIVATED K+
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