US EPA

2312652 

Journal Article 

Effects Of Methylmercury (MeHg) On GABAA Receptor-Mediated Currents In HEK-293 Cells Are Not Altered By The Presence Of The alpha6 Subunit 

Herden, CJ; Hajela, RK; Yuan, Y; Atchison, WD 

2006 

1 

Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 

TOX/6002316 

90 

1-S 

eng 

Differential expression of the GABAA receptor alpha1 and alpha6 subunit has been hypothesized to be responsible for the differential effects of MeHg observed in cerebellar granule and Purkinje neurons. To test this hypothesis, we investigated the effects of MeHg on HEK-293 cells transfected with an expression cDNA clone from rat for either the alpha1 or alpha6 subunit of the GABAA receptor in conjunction with a beta2 and gamma2 subunit. GABA-mediated currents (IGABA) were obtained using the whole-cell voltage- clamp technique and a symmetrical [Cl -]. MeHg (1.0 and 10 uM) blocked IGABA in a time- and concentration-dependent manner in cells containing GABAA receptors with either the alpha1 or alpha6 subunit. Time to block of IGABA by MeHg did not differ significantly between cells containing the two receptor subtypes. Moreover, MeHg (10 uM) caused a prolongation of IGABA slow decay rate in cells containing either receptor subtype. This prolongation appeared to be more pronounced in cells containing the alpha6-receptor subtype. Additionally, the time-course of development of slow decay prolongation by MeHg did not differ between the two receptor subtypes. In both, the onset to slow decay prolongation occurred within 60 s and the peak effect occurred by 550 s. These results suggest that differential expression of GABAA receptor ?1 or ?6 subunits alone may not underlie the differential effects of MeHg on GABAergic function observed in cerebellar cells; other factors may be involved as well.