Figure 8.

Schematic of the proposed impact of heterozygous potassium channel subfamily K member 3 (KCNK3) mutation in pulmonary arterial hypertension (PAH). Wildtype KCNK3 (light blue) and mutant (“PAH”) KCNK3 (dark blue) homomeric, and heterodimeric channels are expressed in human lung. Additional interactions of KCNK3 with KCNK9 (brown) channel subunits occur outside of the lung, protecting against KCNK3 loss of function. However, in human pulmonary artery smooth muscle cells (hPASMCs), only KCNK3 (and not KCNK9) is expressed, and the greater proportion of mutant KCNK3 channels in hPASMCs promotes membrane depolarization. ONO‐RS‐082, a KCNK3 activator, recovers function of some mutant and wildtype KCNK3 channels leading to PASMC hyperpolarization, which may represent a therapeutic avenue in PAH. PAH indicates pulmonary arterial hypertension; PASMC, pulmonary artery smooth muscle cell; WT, wildtype.