This heterodimeric toxin potently activates mouse acid-sensing ion channel ASIC1,ACCN2 expressed in Xenopus oocytes. Both alternatively spliced isoforms ASIC1a and ASIC1b are activated, with a higher potency for ASIC1a (EC(50)=9.4 nM) vs ASIC1b (EC(50)=23 nM). The ASIC3,ACCN3 subtype is also sensitive to the heterodimer, but with a lower potency (EC(50)=830 nM). On ASIC2a,ACCN1, the toxin shows a very weak activation, but produces a remarkable potentiation (>100-fold) of protons when the extracellular pH drops below neutrality. The toxin interacts with the extracellular region of the channel, since responses are only observed in the outside-out configuration. In vivo, the heterodimer elicits robust pain-related behavior in mice by activation of ASIC1,ACCN2 channels on capsaicin-sensitive nerve fibers
"A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain."Bohlen C.J., Chesler A.T., Sharif-Naeini R., Medzihradszky K.F., Zhou S., King D., Sanchez E.E., Burlingame A.L., Basbaum A.I., Julius D.Nature 479:410-414(2011)
Research Topic:Others
