Insertion of a SNS‐specific tetrapeptide in S3–S4 linker of D4 accelerates recovery from inactivation of skeletal muscle voltage‐gated Na channel μ1 in HEK293 cells

Abstract

Na channel subunits αSNS (PN3) and αμ1(SkM1) produce slowly inactivating/TTX‐resistant and rapidly inactivating/TTX‐sensitive currents, respectively. αSNS (PN3) current recovers from inactivation (reprimes) rapidly. Sequence alignment identified the tetrapeptide SLEN, in the S3–S4 linker of D4, as αSNS‐specific. To determine whether SLEN endows Na channels with slow kinetics and/or rapid repriming, we analyzed the transient Na current produced by a chimera μ1SLEN in HEK293 cells. Neither kinetics nor voltage dependence of activation and inactivation was affected. However, repriming was twice as fast as in the wild type at −100 mV. This suggests that SLEN may contribute to the rapid repriming of TTX‐resistant Na current.