Commentary: A BK (Slo1) channel journey from molecule to physiology

Citation: Tricarico D and Mele A (2017) Commentary: A BK (Slo1) channel journey from molecule to physiology. and co-authors in their review paper deal with the hallmarks of big Ca 2+-activated K + (BK) channel biophysics and its physiological impact on specific cells and tissues, highlighting its relationship with auxiliary subunit expression (Contreras et al., 2013). However, the molecular aspects and role of skeletal muscle BK channel subtypes were not extensively discussed. One of the scientific programs running in our laboratories is related to the role of BK channel in native skeletal muscle fibers using patch-clamp in excised patch mode and molecular biology techniques. Briefly, in skeletal muscle the opening of BK channel triggered by depolarization and Ca 2+ ions increases the duration of the hyperpolarization phase between bursts of action potentials reducing the firing capability during discharge. One important aspect concerns the BK channel diversity in the tissues. In fact, the functional diversity of BK channel is established by the association of the alpha subunit encoded by KCNMA1 gene with auxiliary β1–β4 subunits encoded by KCNMB1–4 genes with the contribution of novel γ subunits (Contreras et al., 2013; Toro et al., 2014; Torres et al., 2014). In skeletal muscle we established that the alternative splicing of the KCNMA1/slo1 gene is the main mechanism regulating BK channel diversity in the muscle phenotypes (Shipston, 2001; Tricarico et al., 2005; Dinardo et al., 2012). Slow-twitch rat fibers show an elevated expression/activity of BK channel which is characterized by a low sensitivity to Ca 2+ ions and absence of response to BK channel openers such as acetazolamide (Tricarico et al., 2004, 2005). In contrast, BK channel of fast-twitch rat fibers show a low expression/activity, high Ca 2+ ions sensitivity, and response to drugs (Tricarico et al., 2004, 2005). The analysis of rat slo1 gene at N1 and C1–C6 splice sites found the presence of 5 different variants in both fast-twitch and slow-twitch muscles, such as e17 in C1, e22, and +29 aa in C2 and rSlo27 and rSlo0 in C4 (Dinardo et al., 2012). Real time-PCR experiment showed that e22 and rSlo0 variants are markedly expressed in fast-twitch muscle, the rSlo27 is found in the slow twitch muscle giving rise to different " types " of BK channels (Dinardo et al., 2012). In skeletal muscle, the different types of BK channel play muscle-specific roles contributing to the calcium-dependent phenotype determination/adaptation to disuse which …