Fig. 3

Role of KCC1 in osteoclasts. On the ruffled border, transport systems shown consist of KCC1, the Cl⁻ channel CLC-7 [95], and the vacuolar H⁺-ATPase pump ATP6V1C1 [96]. On the basolateral membrane, they consist of the Na⁺/K⁺-ATPase pump ATPA1B1 [97] and the Cl⁻/HCO₃⁻ exchanger SLC4A2 [98]. On the ruffled border, the role of KCC1 could be to use the K⁺ gradient generated by the Na⁺ pump to provide an accessory route for Cl⁻ secretion in resorptive pits [18]. If, alternatively, KCC1 was localized on the basolateral side, it could then serve two purposes. The first one would be to sustain Cl⁻/HCO₃⁻ exchange by providing the antiporter with a continued supply of Cl⁻ ions. The presence of KCC1 at this location would thus allow secondarily for higher H⁺_i and luminal H⁺ secretion. The second one would be to sustain Na⁺/K⁺-ATPase activity by providing the enzyme with a continued supplied of K⁺ ions. The presence of KCC1 at this location would thus allow secondarily for higher intracellular negativity and luminal Cl⁻ secretion