Fig. 1.

Characterization of human Clcn2 gene variants in primary aldosteronism and the op allele. a ClC-2 topology model, based on the CLC crystal structure⁶⁶, mapping positions of genetic variants found in early-onset primary aldosteronism^22,23. N-terminal and J-K linker domains previously shown^27,28 to be important for opening ClC-2 are highlighted in red. b–l Representative current traces obtained by two-electrode voltage clamp of Xenopus oocytes injected with the indicated ClC-2 cRNAs. Voltage clamp protocol indicated in the inset of panel b. The rodent “op” mutant exactly mimics the channel encoded by the Clcn2^op allele in the present knock-in mouse model. For comparison to the human G24D mutant, the equivalent G30D rodent mutant was measured. In some experiments (f, g) individual ClC-2(R172Q)-expressing oocytes (n = 7) were first measured with ND109, pH 7.4 and then in ND109 buffered to pH 8.5. m Plot of mean current measured at 2 s after clamping to indicated voltages and (n) individual currents at a clamp of −80 mV for experiments of b–l. The number of cells measured is indicated in parenthesis. m, n Currents are presented as mean ± SEM