1.A.1.3.10
Calcium-, magnesium- and voltage-activated K⁺ channel, Slo1 (Kcma1; KCNMA, KCNMA1), a BK channel, of 1236 aas and 6 N-terminal TMSs. Its activation dampens the excitatory events that elevate the cytosolic Ca²⁺ concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential, and it plays a key role in controlling excitability in a number of systems. Ethanol and carbon monoxide-bound heme increase channel activation while heme inhibits channel activation (Tang et al. 2003). The molecular structures of the human Slo1 channel in complex with beta4 has been solved revealing four beta4 subunits, each containing two transmembrane helices, encircling Slo1, contacting it through helical interactions inside the membrane. On the extracellular side, beta4 forms a tetrameric crown over the pore. Structures with high and low Ca²⁺ concentrations show that identical gating conformations occur in the absence and presence of beta4, implying that beta4 serves to modulate the relative stabilities of 'pre-existing' conformations rather than creating new ones (Tao and MacKinnon 2019). BK channels show increased activities in Angelman syndrome due to genetic defects in the ubiquitin protein ligase E3A (UBE3A) gene (Sun et al. 2019). It is a large-conductance potassium (BK) channel that can be synergistically and independently activated by membrane voltage and intracellular Ca²⁺. The only covalent connection between the cytosolic Ca²⁺-sensing domain and the TM pore and voltage sensing domains is a 15-residue 'C-linker' which plays a direct role in mediating allosteric coupling between BK domains (Yazdani et al. 2020).  Site specific deacylation by the alpha/beta acyl-hydrolase domain-containing protein 17A, ABHD17a (Q96GS6, 310 aas), controls BK channel splice variant activity (McClafferty et al. 2020).