ASIC2 Synergizes with TRPV1 in the Mechano-Electrical Transduction of Arterial Baroreceptors

Mechanosensitive ion channels(MSCs)are key molecules in the mechano-electrical transduction of arterial baroreceptors.Among them,acid-sensing ion channel 2(ASIC2)and transient receptor potential vanilloid subfamily member 1(TRPV1)have been studied extensively and documented to play important roles.In this study,experiments using aortic arch-aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary,as blocking either abrogated nearly all pressure-dependent neural discharge.However,whether ASIC2 and TRPV1 work in coordination remained unclear.So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV 1 only partially blocked these currents.Immunofluorescence staining of aortic arch-aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings,and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors.Moreover,protein modeling analysis,exogenous co-immunoprecipitation assays,and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly.In summary,our research suggests that ASIC2 and TRPV1 form a compact complex and function synergisti-cally in the mechano-electrical transduction of arterial baroreceptors.The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV 1.