Influence of external and intracellular pH on propofol-induced responses in rat locus coeruleus neurons

The effect of external and intracellular pH on propofol-induced responses in rat locus coeruleus neurons was examined using intracellular recording from in vitro brain slice preparations. Experimental variation of external pH from 7.34 to 6.81 did not affect the propofol-induced responses. In contrast, raising the external pH from 7.34 to 8.10 resulted in enhanced 100 μM propofol effects. The effects were 1.8 times greater on membrane hyperpolarization (pH 8.10: 11.8 ± 1.3 mV; pH 7.34: 6.5 ± 1.0 mV, n = 5) and 1.5 times greater on reduction in input resistance (pH 8.10: 38.2 ± 6.3%; pH 7.34: 24.7 ± 4.1%, n = 5). Cytosolic acidification was used in which 1/3 NaCl in artificial cerebrospinal fluid was replaced with weak organic acids–sodium acetate. It did not significantly affect the propofol-induced responses. On the other hand, intracellular alkalinization with 5 mM NH4Cl markedly suppressed the 100 μM propofol-induced membrane hyperpolarization (1.0 ± 0.6 mV; control: 13.9 ± 0.9 mV, n = 5) and reduction of input resistance (38.1 ± 1.3%; control: 61.0 ± 4.3%, n = 5). However, the presence of 3–5 mM ammonium acetate also showed the similarly suppressing effect on membrane hyperpolarization (1.7 ± 0.6 mV; control: 9.2 ± 1.8 mV, n = 5) and reduction of input resistance (28.5 ± 8.5%; control: 37.0 ± 6.3%, n = 5) caused by 100 μM propofol. We suggested that the main suppressing effect of NH4Cl results from ammonium ion, but not intracellular alkalinization. Furthermore, we examined the feature of pharmacological regulation of propofol-induced responses by pentobarbital or alphaxalone during pH changes. It appears that neither pentobarbital nor alphaxalone could allosterically modulate the propofol-induced responses, which had been affected by pH changes.