The pathogenesis of Brugada Syndrome (BrS) has been associated with mutations in the cardiac sodium channel gene SCN5A, resulting in loss-of-function. Recently, the L325R mutation has been proposed to cause BrS through a dominant-negative effect. Dominant-negative effects are usually the consequence of mutant subunits assembling with wild-type (WT) into non-functional channel multimers. In contrast, sodium channel α-subunits are not believed to oligomerize. However, there is increasing evidence suggesting the existence of α-α interactions between sodium channels. Therefore, we tested whether the dominant-negative effect seen in some BrS mutations is due to interactions between sodium channel α-subunits. We co-expressed a dominant-negative BrS mutation, L325R, with WT channels at different molar ratios. Channels containing the mutation alone did not elicit current. When WT and L325R channels were co-transfected in a 1:1 and 4:1 WT:L325R ratios, the normalized peak INa densities were reduced respectively to 29.8±6.2% and 57.3±5.8% of the control WT confirming the dominant-negative effect of this mutation. When using a binomial distribution, our results were fitted best by a configuration suggesting the interaction of two channel monomers. We also investigated the existence of channel-channel interactions using the BrS mutation L567Q. This mutation displays biophysical alterations possibly too small to explain the clinical phenotype. Interestingly, co-expression of L567Q with WT channels produced a significant reduction in INa density which could possibly also be caused by channel-channel interactions and therefore explain the clinical manifestation of the disease. In conclusion, our experiments using BrS mutations, now suggest the idea of a dimerization of sodium channel α-subunits.