Summary of the inhibitory effects of isoflurane under heterozygous conditions and the impact of A341V on current density. (A) Summary of the inhibitory effects of isoflurane on 2KCNQ1 + KCNE1 and A341V + KCNQ1 + KCNE1 at +60 mV. Similar to the homozygous conditions (fig. 2), the A341V mutant was significantly more susceptible to the inhibitory effects of isoflurane (n = 11–13, *P < 0.01 vs. 2KCNQ1 + KCNE1). (B) The current–voltage relationships under control (isoflurane-free) conditions. Current amplitudes were normalized to cell capacitance to yield current density. A341V + KCNQ1 + KCNE1 exhibited significantly smaller current density than the corresponding wild-type IKs, 2KCNQ1 + KCNE1, and KCNQ1 + KCNE1 (n = 11–13, *P < 0.01 vs. 2KCNQ1 + KCNE1, P < 0.05 vs. KCNQ1 + KCNE1; §P < 0.05 vs. 2KCNQ1 + KCNE1 and KCNQ1 + KCNE1). This is suggestive of a dominant negative effect by A341V.