Figure 6. Interaction between ASICs and lactate due to hypoxia and hyperosmolarity in the SON.

A, typical changes in membrane potential elicited by decreasing pH from 7.4 to 6.8 in the presence or absence of lactate. Activation of ASIC current by pH 6.8 transiently depolarized the neurons. When pH 6.8 external solution with 15 mm lactate was applied, the neuron was depolarized with a train of action potentials at the initial transient depolarization. B, when cells were held at a level just around the firing threshold with a current injection, pH 6.8 induced depolarization and action potentials followed by a refractory period. Inset: lactate increased the depolarization and firing number induced by pH 6.8. The scale bar is 50 mV/1 s. C, hypertonicity stimulated production of La⁻ in the SON tissue but not production of pyruvate. D, the tissue La⁻ level in the SON was significantly increased after osmotic stimulation resulting from salt loading by drinking 2% NaCl for 5 days whereas the tissue pyruvate level was markedly decreased after osmotic stimulation. The tissue La⁻:pyruvate ratio was also increased in the SON of salt-loaded rats. E, the SON segment incubated under hypoxic conditions with 85% N₂–10% O₂–5% CO₂ showed higher La⁻ secretion and lower pyruvate secretion than the segment in normoxic conditions with 95% air–5% CO₂. The La⁻:pyruvate ratio in the medium released from SON was significantly increased under hypoxia.