Profiling of GABAA and GABAB receptor expression in the myometrium of the human uterus.

ABSTRACT

AIMS: γ-aminobutyric acid (GABA) mediates its physiological effects through the GABAA and GABAB receptors. In this study the putative expression of GABAAR and GABABR subunits in human myometrium tissue was investigated. MAIN METHODS: The expression levels of the 19 GABAAR subunits (α1-α6, ß1-ß3, γ1-γ3, δ, ε, π, θ, ρ1-ρ3) and the three GABABR subunits (GABAB1a, GABAB1b, GABAB2) were characterized by RT-qPCR analysis on two commercial samples and six samples derived from surgically removed myometrial tissues from different women. We probed for functional GABAAR expression in primary human myometrial smooth muscle cells (HMSMCs) by whole-cell patch-clamp electrophysiology. KEY FINDINGS: The absolute mRNA levels of the 22 GABAAR and GABABR genes varied considerably across the eight samples, but a pronounced overlap existed between the specific subunits detected in the samples, with α2, ß2, ß3, ε, π, θ, GABAB1a and GABAB1b mRNAs being detected in most samples. The expression profile of GABAAR and GABABR subunit mRNAs in HMSMCs correlated with that observed in the eight tissue samples, albeit the subunit transcripts were detected at lower relative levels. Neither muscimol nor GABA evoked significant currents in these cells in the patch-clamp recordings. SIGNIFICANCE: While the expression of the GABAB1 subunits on their own is unlikely to give rise to functional GABABR expression, the GABAAR subunits identified at mRNA level would be able to form functional receptors in the human myometrial tissue. Although GABAAR-mediated currents could not be recorded from HMSMCs in this study, this suggests a role for GABAergic transmission in the human myometrium.