Extended Data Fig. 6: The MET and adult-like potassium currents are normal in Ikzf2^cello mice.

a, b, MET currents were recorded from OHCs of P9 Ikzf2^cello/cello and Ikzf2^cello/+ (control) littermates. During voltage steps, hair bundles were displaced by applying a 50-Hz sinusoidal force stimuli (the driver voltage to the fluid jet is shown above the traces)³⁹. At hyperpolarized membrane potentials (−121 mV), saturating excitatory bundle stimulation (that is, towards the taller stereocilia) elicited a large inward MET current from both Ikzf2^cello/+ and Ikzf2^cello/cello OHCs, whereas inhibitory bundle stimulation (that is, away from the taller stereocilia) closed the MET channels and reduced the resting current. Because the MET current reverses near 0 mV, it became outward when excitatory bundle stimulation was applied during voltage steps positive to its reversal potential. At positive membrane potentials (+99 mV), excitatory bundle stimulation now elicited similar outward MET currents with larger resting amplitudes. Arrows indicate closure of the MET channels (that is, disappearance of the resting current) during inhibitory bundle displacements, arrowheads indicate the larger resting MET current at +99 mV compared to −121 mV. c, Peak-to-peak current–voltage curves obtained from Ikzf2^cello/+ (n = 10 biologically independent samples) and Ikzf2^cello/cello (n = 8 biologically independent samples) OHCs at P9. The maximal MET current and the resting open probability of the MET channel were found to be similar between the two genotypes. Data are mean ± s.e.m. d, e, Total K⁺ currents recorded from P18 Ikzf2^cello/+ control (d) and Ikzf2^cello/cello mutant (e) OHCs. The size of the K⁺ current, which is mainly due to the negatively activated I_K,n (in addition to a small delayed rectifier I_K¹⁵), was smaller in Ikzf2^cello/cello OHCs. f, Average peak current–voltage relationship for the total K⁺ current recorded from the OHCs of Ikzf2^cello/+ (n = 9 OHCs from 6 biologically independent animals) and Ikzf2^cello/cello (n = 7 OHCs from 5 biologically independent animals) mice at P16–P18. Data are mean ± s.e.m. g, h, After normalization to the significantly reduced surface area of Ikzf2^cello/cello OHCs (for this set of experiments: Ikzf2^cello/+: 14.2 ± 0.4 pF; Ikzf2^cello/cello: 11.2 ± 0.5 pF; P < 0.0005), both the total I_K (g) and isolated I_K,n (h) were not significantly different between the two genotypes at P16–P18 (two-sided Welch’s t-test). Data are mean ± s.e.m. i, NanoString validations of genes downregulated in P8 Ikzf2^cello/cello cochleae at P16, normalized to wild-type reads. Data are mean ± s.d. (n = 4 biologically independent samples per genotype). *P = 0.038 (Ppp17r1 in Ikzf2^cello/cello vs Ikzf2^+/+), *P = 0.037 (Ppp17r1 in Ikzf2^cello/cello vs Ikzf2^cello/+) (two-sided Welch’s t-test).