Time- and state-dependent effects of methanethiosulfonate ethylammonium (MTSEA) exposure differ between heart and skeletal muscle voltage-gated Na+ channels

► ► Wild-type hNav1.5 reacts readily with MTSEA, reducing INa. ► The mutant hNav1.5-C373Y in the closed state does not react with MTSEA. ► When inactivated (fast or slow), hNav1.5-C373Y does react with MTSEA after 4 min. ► The isoform hNav1.4 does not show the MTSEA effect. ► Molecular and/ or kinetic differences between the isoforms may explain the results.