Background: The gamma aminobutyric acid type A (GABA(A)) receptor is a prime target of many anesthetics, including midazolam and propofol. Although these anesthetics have sedative and hypnotic properties by enhancing GABA(A) receptor activity, their interactions at the GABA(A) receptors have not been explored. We investigated the interaction of midazolam and propofol with α(1)β(2)γ(2)L and α(1)β(2)γ(2)S GABA(A) receptors.
Methods: Using the whole-cell patch clamp technique, we tested the effects of midazolam and propofol on GABA-induced currents in human embryonic kidney 293 T cells transfected with α(1)β(2)γ(2)L and α(1)β(2)γ(2)S GABA(A) receptors.
Results: Midazolam and propofol on their own enhanced the amplitude of GABA(A) receptor responses in a dose-dependent manner, and they had additive effects on α(1)β(2)γ(2)S GABA(A) receptors, but not on α(1)β(2)γ(2)L GABA(A) receptors. However, additive interactions of midazolam and propofol on the α(1)β(2)γ(2)L GABA(A) receptors were observed when protein kinase C was inhibited.
Conclusions: The interaction between midazolam and propofol is affected by receptor subtype, and protein kinase phosphorylation influences their interaction on the α(1)β(2)γ(2)L receptor.
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