We have shown that BK channels are regulated by a number of signaling pathways, by PKG (Robertson et al., 1993;Gribkova et al., 2002), by PKA (Schubert et al., 1996), by PKC (Schubert et al., 1999b;Mladenov et al., 2008) as well as intracellular pH (Petkova-Kirova et al., 2000;Schubert et al., 2001). In small arteries, these signaling pathways mediate the contribution of BK channels to NO- and iloprost-induced dilations (Schubert et al., 1997;Sausbier et al., 2000;Sausbier et al., 2005;Climent et al. 2012;Iozzi et al. 2013), to ghrelin- (Mladenov et al., 2008) and methoxamine-induced vasocontraction, where the latter was shown to increase with postnatal maturation (Shvetsova et al., 2019; Ma et al., 2020) as well as to the setting of the level of myogenic tone (Wesselman et al., 1997;Schubert et al., 1999a; Ma et al., 2020). Interestingly, when the full range of vessel tone was explored, NO-induced dilations were shown to be limited by BK channels, only at high levels of vessel tone BK channels facilitate this dilation (Schmid et al., 2018). All these findings were obtained on different small arteries from rats and PKG- as well as BK channel-deficient mice. Some of these data have been summarized in a review article (Schubert & Nelson, 2001).

Further, we could demonstrate that inwardly rectifying potassium (Kir2) channels are activated by NO, where this effect contributes to the NO-induced dilation of small arteries (Schubert et al., 2004) and that the negative feedback regulation of vasocontraction by Kir2 channels decreases during postnatal maturation (Shvetsova et al., 2019).

Ongoing studies are focused on the biophysical and pharmacological properties of several voltage-operated potassium channels and their function in the cardiovascular system. It was found that Kv7 channels contribute to the vasodilating effect of factors released from periadventitial fat (Schleifenbaum et al., 2010; Zavaritskaya et al., 2013, Tsvetkov et al., 2016), lose their dominating role in the negative feedback regulation of vasocontraction during postnatal maturation (Shvetsova et al., 2019; Ma et al., 2020) and are limited in their role as negative feedback on vasoconstriction by BK channels (Ma et al., 2020). These channels share with BK channels the ability to mediate vasodilation by the novel K channel opener GoSlo (Zavaritskaya et al., 2020). Overviews of the tools to study Kv7 channels and of the role of different K channels in early postnatal maturation have been presented in reviews (Gollasch et al., 2018; Svetsova et al., 2021).

Recently it was shown that another, less well studied class of K channels, TASK-1 channels, also lose their ability to mediate negative feedback regulation on vasocontraction during postnatal maturation (Shvetsova et al., 2020).

References

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