Preferred mexiletine block of human sodium channels with IVS4 mutations and its pH-dependence

B Mohammadi, K Jurkat-Rott, A Alekov… - Pharmacogenetics …, 2005 - journals.lww.com
The effects of extracellular pH (6.2, 7.4 and 8.2) and 0.1 mM mexiletine, a channel blocker of
the lidocaine type, are studied on two mutations of the fourth voltage sensor of the Na v 1.4
sodium channel, R1448H/C. The fast inactivated channel state to which mexiletine
preferentially binds is destabilized by the mutations. By contrast to the expected low
response of R1448H/C carriers, mexiletine is particularly effective in preventing exercise-
induced stiffness and paralysis from which these patients suffer. Our measurements …