Biological activity |
Hm1a is a gating modifier toxin that principally inhibits inactivation of the mammalian voltage-gated sodium channel Nav1.1/SCN1A. When tested against human Nav1.1/SCN1A-Nav1.8/SCN10A alpha subunits heterologously expressed in Xenopus oocytes, the toxin inhibits inactivation of Nav1.1 (EC(50)=38 nM), with substantially weaker effects on Nav1.2/SCN2A (EC(50)=236 nM) and Nav1.3/SCN3A (EC(50)=220 nM). The toxin inhibits several subtypes of voltage-gated potassium channels with significantly lower potency than its effects on Nav1.1/SCN1A (PubMed:27281198). It is a moderately potent blocker of Kv2.1/KCNB1, Kv2.2/KCNB2, Kv4.1/KCND1, Kv4.2/KCND2 and Kv4.3/KCND3 and has little effect on Kv1.1/KCNA1, Kv1.2/KCNA2, Kv1.3/KCNA3, Kv1.4/KCNA4, Kv1.5/KCNA5, Kv1.6/KCNA6 and Kv3.4/KCNC4. IC50 is 280 nM on Kv4.1/KCND1, whereas percentage of current inhibition are 23% on Kv2.1/KCNB1 at 100 nM, 19.7% on Kv2.2/KCNB2 at 100 nM (and 51% at 300 nM), 39% on Kv4.2/KCND2 at 300 nM, and 43% on Kv4.3/KCND3 at 300 nM. It does not inhibit Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.6/SCN8A, Nav1.7/SCN9A, and Nav1.8/SCN10A at concentrations up to 1 µM. |