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 GABA_A and GABA_B receptors. In this study the putative expression of GABA_AR and GABA_BR subunits in human myometrium tissue was investigated.

Main methods: The expression levels of the 19 GABA_AR subunits (α₁-α₆, β₁-β₃, γ₁-γ₃, δ, ε, π, θ, ρ₁-ρ₃) and the three GABA_BR subunits (GABA_B1a, GABA_B1b, GABA_B2) 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 GABA_AR expression in primary human myometrial smooth muscle cells (HMSMCs) by whole-cell patch-clamp electrophysiology.

Key findings: The absolute mRNA levels of the 22 GABA_AR and GABA_BR genes varied considerably across the eight samples, but a pronounced overlap existed between the specific subunits detected in the samples, with α₂, β₂, β₃, ε, π, θ, GABA_B1a and GABA_B1b mRNAs being detected in most samples. The expression profile of GABA_AR and GABA_BR 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 GABA_B1 subunits on their own is unlikely to give rise to functional GABA_BR expression, the GABA_AR subunits identified at mRNA level would be able to form functional receptors in the human myometrial tissue. Although GABA_AR-mediated currents could not be recorded from HMSMCs in this study, this suggests a role for GABAergic transmission in the human myometrium.

Keywords: GABA(A) receptor; GABA(B) receptor; Myometrium; RT-qPCR; Uterus.