Tetraethylammonium block of the BNC1 channel

The brain Na+ channel-1 (BNC1, also known as MDEG1 or ASIC2) is a member of the DEG/ENaC cation channel family. Mutation of a specific residue (Gly430 ) that lies N-terminal to the second membrane-spanning domain activates BNC 1 and converts it from a Na+-selective channel to one permeable to both Na and K+. Because all K+ channels are blocked by tetraethylammonium (TEA), w e asked if TEA would inhibit BNC1 with a mutation at residue 430. External TEA blocked BNC1 when residue 430 was a Val or a Thr. Block was steeply vol tage-dependent and was reduced when current was outward, suggesting multi-i on block within the channel pore. Block was dependent on the size of the qu aternary ammonium; the smaller tetramethylammonium blocked with similar pro perties, whereas the larger tetrapropylammonium had little effect. When res idue 430 was Phe, the effects of tetramethylammonium and tetrapropylammoniu m were not altered. In contrast, block by TEA was much less voltage-depende nt, suggesting that the Phe mutation introduced a new TEA binding site loca ted similar to 30% of the way across the electric field. These results prov ide insight into the structure and function of BNC1 and suggest that TEA ma y be a useful tool to probe function of this channel family.