Figure 6.
Figure 6. Comparison of the shift of the inactivation curve by carbamazepine and the other anticonvulsant drugs in the wild-type and different Y1618 mutant channels. The inactivating pulse duration was 9 s to make sure of steady-state binding of the anticonvulsants, which have relatively slow binding rates onto the channel. (A) Representative inactivation curves in different Y1618 mutant channels before (open circles) and after (closed circles) the application of 300 μM carbamazepine. The lines are fits with a Boltzmann function with V1/2 values (control vs. 300 μM carbamazepine) in mV of −54.4 versus −64.9, −62.2 versus −66.1, −71.5 versus −75.5, −54.7 versus −60.6, and −62.0 versus −74.6, and k values (control vs. carbamazepine) of 4.3 versus 4.5, 5.7 versus 5.7, 5.4 versus 5.7, 5.0 versus 8.3, and 4.5 versus 5.2 for the wild-type (WT), Y1618K, Y1618D, Y1618R, and Y1618W mutant channels, respectively. The shift (ΔV) of the inactivation curve is defined as the difference between the V1/2 values in 300 μM carbamazepine and the V1/2 value in control and is shown in the bar graph. Mutations Y1618K, Y1618D, and Y1618R, but not Y1618W, evidently decrease the shift of the inactivation curve by carbamazepine (n = 3–4). ***, P < 0.005 by Student’s t test (compared with the wild-type data). (B) The shift of the inactivation curve by phenytoin and lamotrigine in the Y1618K mutant channel. The top panels show two representative oocytes containing the wild-type channel (left) and the Y1618K mutant channel (right), respectively. In the Y1618K mutant channel, the leftward shift of the inactivation curve by 100 μM lamotrigine (LMT), 100 μM phenytoin (DPH), or 300 μM carbamazepine (CBZ) is evidently smaller than that in the wild-type channel. Two sets of control data (control I and II, respectively; open symbols) were obtained before and after drug application in each plot to show no voltage drift during this long experiment. The lines are fits with a Boltzmann function. The averaged shift (ΔV) of the inactivation curve by 100 μM lamotrigine, phenytoin, or carbamazepine is shown in the bar graph (n = 4–5). **, P < 0.05 and ***, P < 0.005 by Student’s t test (compared with the wild-type data with 100 μM carbamazepine).

Comparison of the shift of the inactivation curve by carbamazepine and the other anticonvulsant drugs in the wild-type and different Y1618 mutant channels. The inactivating pulse duration was 9 s to make sure of steady-state binding of the anticonvulsants, which have relatively slow binding rates onto the channel. (A) Representative inactivation curves in different Y1618 mutant channels before (open circles) and after (closed circles) the application of 300 μM carbamazepine. The lines are fits with a Boltzmann function with V1/2 values (control vs. 300 μM carbamazepine) in mV of −54.4 versus −64.9, −62.2 versus −66.1, −71.5 versus −75.5, −54.7 versus −60.6, and −62.0 versus −74.6, and k values (control vs. carbamazepine) of 4.3 versus 4.5, 5.7 versus 5.7, 5.4 versus 5.7, 5.0 versus 8.3, and 4.5 versus 5.2 for the wild-type (WT), Y1618K, Y1618D, Y1618R, and Y1618W mutant channels, respectively. The shift (ΔV) of the inactivation curve is defined as the difference between the V1/2 values in 300 μM carbamazepine and the V1/2 value in control and is shown in the bar graph. Mutations Y1618K, Y1618D, and Y1618R, but not Y1618W, evidently decrease the shift of the inactivation curve by carbamazepine (n = 3–4). ***, P < 0.005 by Student’s t test (compared with the wild-type data). (B) The shift of the inactivation curve by phenytoin and lamotrigine in the Y1618K mutant channel. The top panels show two representative oocytes containing the wild-type channel (left) and the Y1618K mutant channel (right), respectively. In the Y1618K mutant channel, the leftward shift of the inactivation curve by 100 μM lamotrigine (LMT), 100 μM phenytoin (DPH), or 300 μM carbamazepine (CBZ) is evidently smaller than that in the wild-type channel. Two sets of control data (control I and II, respectively; open symbols) were obtained before and after drug application in each plot to show no voltage drift during this long experiment. The lines are fits with a Boltzmann function. The averaged shift (ΔV) of the inactivation curve by 100 μM lamotrigine, phenytoin, or carbamazepine is shown in the bar graph (n = 4–5). **, P < 0.05 and ***, P < 0.005 by Student’s t test (compared with the wild-type data with 100 μM carbamazepine).

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal