Identification of a Novel Protein Complex Containing ASIC1a and GABA(A) Receptors and Their Interregulation

Acid-sensing ion channels (ASICs) belong to the family of the epithelial sodium channel/degenerin (ENaC/DEG) and are activated by extracellular protons. They are widely distributed within both the central and peripheral nervous systems. ASICs were modified by the activation of γ-aminobutyric acid receptors (GABA(A)), a ligand-gated chloride channels, in hippocampal neurons. In contrast, the activity of GABA(A) receptors were also modulated by extracellular pH. However so far, the mechanisms underlying this intermodulation remain obscure. We hypothesized that these two receptors-GABA(A) receptors and ASICs channels might form a novel protein complex and functionally interact with each other. In the study reported here, we found that ASICs were modified by the activation of GABA(A) receptors either in HEK293 cells following transient co-transfection of GABA(A) and ASIC1a or in primary cultured dorsal root ganglia (DRG) neurons. Conversely, activation of ASIC1a also modifies the GABA(A) receptor-channel kinetics. Immunoassays showed that both GABA(A) and ASIC1a proteins were co-immunoprecipitated mutually either in HEK293 cells co-transfected with GABA(A) and ASIC1a or in primary cultured DRG neurons. Our results indicate that putative GABA(A) and ASIC1a channels functionally interact with each other, possibly via an inter-molecular association by forming a novel protein complex.