Fig. 6.
Inhibitory effects of bupivacaine on sodium ion currents in transiently transfected human embryonic kidney (HEK)-293T cells with and without 1-oleoyl-2-acetyl-sn-glycerol, an activator of transient receptor potential canonical (TRPC) channels. (A, B) Representative sodium ion currents in the same cell perfused sequentially with standard solution (left), 3 μM bupivacaine (center), and 3 μM bupivacaine plus 100 μM 1-oleoyl-2-acetyl-sn-glycerol (right) in HEK-293T cells transfected with cardiac sodium channels (Nav1.5) alone (A), and HEK-293T cells transfected with Nav1.5 and TRPC3 (B). The voltage protocol is shown in the inset. (C) Sodium ion currents were reduced by 3 μM bupivacaine while there was no further reduction caused by 1-oleoyl-2-acetyl-sn-glycerol in HEK-293T cells transfected with Nav1.5 alone (n = 4 cells; 89.5 ± 3.2% and 89.1 ± 4.5% of control, respectively; P = 0.617). On the other hand, there were further reductions caused by 1-oleoyl-2-acetyl-sn-glycerol in HEK-293T cells cotransfected with Nav1.5 and TRPC3 (n = 4 cells; 85.9 ± 7.4% and 72.2 ± 6.5% of control, respectively; P = 0.048). There was a significant difference between Nav1.5 alone group and Nav1.5 with TRPC3 group in sodium ion current reduction caused by bupivacaine and 1-oleoyl-2-acetyl-sn-glycerol (n = 4 cells per group; P = 0.006). Data are mean ± SD. *P < 0.05 indicates significant differences between bupivacaine alone and coapplication of bupivacaine + 1-oleoyl-2-acetyl-sn-glycerol. ‡P < 0.01 indicates a significant difference between HEK-293T cells transfected with Nav1.5 alone, and HEK-293T cells transfected with Nav1.5 and TRPC3. TRPC, transient receptor potential canonical