The effect of TZDs on peak INa and NaV inactivation
| Experimental condition | Inhibition of peak INa | |||||||||
| Prepulse to V0 | Prepulse to V1/2 | V1/2 of NaV inactivation | ||||||||
| norm INa | SD | norm INa | SD | n | V1/2 (mV) | SD | n | ΔV1/2 | SD | |
| Control | 1.00 | # | 1.00 | # | 7 | −68 | 2.3 | 6 | −13 | 4.1 |
| 6 µM troglitazone | 0.62a | 0.12 | 0.36a | 0.13 | 7 | −81a | 4.8 | 6 | ||
| Wash | 0.97 | 0.05 | 0.79 | 0.08 | 7 | −73a | 1.8 | 4 | ||
| Control | 1.00 | # | 1.00 | # | 3 | −70 | 1.9 | 3 | −5 | 1.5 |
| 200 µM rosiglitazone | 0.74b | 0.04 | 0.60b | 0.04 | 3 | −76c | 1.5 | 3 | ||
| Wash | 0.97 | 0.01 | 0.76 | 0.03 | 3 | −76 | 2.1 | 3 | ||
| Control | 1.00 | # | 1.00 | # | 4 | −72 | 2.8 | 4 | −2 | 0.4 |
| 10 µM pioglitazone | 0.97 | 0.02 | 0.91b | 0.01 | 4 | −74b | 2.5 | 4 | ||
| Wash | 1.01 | 0.05 | 0.89 | 0.11 | 4 | −75c | 3.0 | 3 | ||
| Control | 1.00 | # | 1.00 | # | 7 | −69 | 1.5 | 4 | −3 | 1.9 |
| 6 µM ciglitazone | 0.74a | 0.03 | 0.72a | 0.11 | 7 | −72c | 0.4 | 4 | ||
| Wash | 0.77 | 0.04 | 0.76 | 0.16 | 7 | −71 | 1.3 | 4 | ||
| Control | n/a | n/a | −68 | 2.5 | 5 | 0.3 | 0.8 | |||
| Sham drug | n/a | n/a | −68 | 2.4 | 5 | |||||
| Experimental condition | Inhibition of peak INa | |||||||||
| Prepulse to V0 | Prepulse to V1/2 | V1/2 of NaV inactivation | ||||||||
| norm INa | SD | norm INa | SD | n | V1/2 (mV) | SD | n | ΔV1/2 | SD | |
| Control | 1.00 | # | 1.00 | # | 7 | −68 | 2.3 | 6 | −13 | 4.1 |
| 6 µM troglitazone | 0.62a | 0.12 | 0.36a | 0.13 | 7 | −81a | 4.8 | 6 | ||
| Wash | 0.97 | 0.05 | 0.79 | 0.08 | 7 | −73a | 1.8 | 4 | ||
| Control | 1.00 | # | 1.00 | # | 3 | −70 | 1.9 | 3 | −5 | 1.5 |
| 200 µM rosiglitazone | 0.74b | 0.04 | 0.60b | 0.04 | 3 | −76c | 1.5 | 3 | ||
| Wash | 0.97 | 0.01 | 0.76 | 0.03 | 3 | −76 | 2.1 | 3 | ||
| Control | 1.00 | # | 1.00 | # | 4 | −72 | 2.8 | 4 | −2 | 0.4 |
| 10 µM pioglitazone | 0.97 | 0.02 | 0.91b | 0.01 | 4 | −74b | 2.5 | 4 | ||
| Wash | 1.01 | 0.05 | 0.89 | 0.11 | 4 | −75c | 3.0 | 3 | ||
| Control | 1.00 | # | 1.00 | # | 7 | −69 | 1.5 | 4 | −3 | 1.9 |
| 6 µM ciglitazone | 0.74a | 0.03 | 0.72a | 0.11 | 7 | −72c | 0.4 | 4 | ||
| Wash | 0.77 | 0.04 | 0.76 | 0.16 | 7 | −71 | 1.3 | 4 | ||
| Control | n/a | n/a | −68 | 2.5 | 5 | 0.3 | 0.8 | |||
| Sham drug | n/a | n/a | −68 | 2.4 | 5 | |||||
The TZD effects on peak INa after prepulses to −130 mV (V0) or to a voltage at which approximately half the channels are in the fast-inactivated state (V1/2). The currents were measured after 1-min perfusion of the drug. Fractional peak INa was normalized to the control value. Right column of the table shows the effects of TZDs on steady-state inactivation (or Na+ channel availability h∞ in the Hodgkin and Huxley, 1952, model). V1/2 values were determined in control after 1-min perfusion of the drug and after 2-min washout of the drug. All TZDs significantly shifted V1/2 toward hyperpolarized potentials. Stimulation protocols as described in detail in Materials and methods and can also be seen in Fig. 10.
P < 0.001 versus control by paired two-tailed Student’s t test.
P < 0.01 versus control by paired two-tailed Student’s t test.
P < 0.05 versus control by paired two-tailed Student’s t test.