Table 2.
Voltage-gated Na+ current densities and properties in neonatal mouse ventricular cardiomyocytes infected with control shRNA, iFGF13 shRNA alone, or with WT or phosphomutant iFGF13-VY-expressing adenoviruses
| INa (pA/pF) | Time to peak (ms) | Time course of inactivation | Voltage dependence of activation | Voltage dependence of inactivation | Recovery from inactivation | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| tfast (ms) | tslow (ms) | Afast/Aslow | V1/2 (mV) | k (mV) | V1/2 (mV) | k (mV) | tfast (ms) | tslow (ms) | |||
| Control shRNA | −51.4 ± 5.1 (23) | 1.03 ± 0.05 (19) | 0.99 ± 0.06 (18) | 4.3 ± 0.3 (18) | 15.5 ± 2.6 (18) | −32.6 ± 0.5 (19) | 7.0 ± 0.2 (19) | −70.7 ± 0.8 (18) | 5.1 ± 0.2 (18) | 3.1 ± 0.3 (16) | 51.1 ± 8.7 (16) |
| iFGF13 shRNA | −54.9 ± 5.7 (23) | 0.92 ± 0.04 (19) | 0.73 ± 0.05 (19) *** | 5.5 ± 0.5 (19) | 27.8 ± 1.9 (19) ** | −36.7 ± 0.8 (19) *** | 7.5 ± 0.3 (19) | −82.8 ± 0.5 (19) **** | 4.9 ± 0.1 (19) | 4.0 ± 0.3 (19) | 45.4 ± 7.5 (19) |
| iFGF13 shRNA + iFGF13-VY-WT | −53.5 ± 4.6 (24) | 0.97 ± 0.03 (23) | 0.84 ± 0.04 (22) | 3.7 ± 0.2 (22) | 16.8 ± 2.6 (22) # | −36.2 ± 0.5 (22) ** | 6.5 ± 0.2 (22) | −74.6 ± 0.8 (22) #### | 4.5 ± 0.1 (22) | 2.7 ± 0.1 (19) | 56.8 ± 8.5 (19) |
| iFGF13 shRNA + iFGF13-VY-35-38A | −56.0 ± 4.8 (21) | 0.90 ± 0.02 (17) | 0.82 ± 0.04 (17) | 3.9 ± 0.2 (17) | 8.4 ± 1.1 (17) #### | −36.1 ± 0.6 (17) * | 6.8 ± 0.2 (17) | −74.6 ± 0.7 (17) #### | 4.9 ± 0.2 (17) | 2.9 ± 0.2 (16) | 44.8 ± 10.0 (16) |
| iFGF13 shRNA + iFGF13-VY-35-38E | −70.1 ± 7.1 (20) | 0.75 ± 0.02 (14) | 0.66 ± 0.03 (12) **** | 3.6 ± 0.2 (12) | 15.2 ± 1.4 (12) # | −36.8 ± 0.7 (14) ** | 7.1 ± 0.2 (14) | −76.9 ± 1.3 (14) ### | 4.8 ± 0.2 (14) | 2.8 ± 0.2 (14) | 61.1 ± 7.1 (14) |
| iFGF13 shRNA + iFGF13-VY-218A | −53.7 ± 5.5 (25) | 0.91 ± 0.03 (20) | 0.86 ± 0.03 (19) | 4.3 ± 0.2 (19) | 18.2 ± 2.3 (19) | −35.0 ± 0.5 (20) | 7.1 ± 0.1 (20) | −75.5 ± 0.8 (20) #### | 4.5 ± 0.1 (20) | 3.4 ± 0.2 (14) | 46.6 ± 3.9 (14) |
| iFGF13 shRNA + iFGF13-VY-218E | −65.9 ± 5.2 (22) | 1.00 ± 0.04 (17) | 0.89 ± 0.05 (17) | 4.5 ± 0.2 (17) | 19.2 ± 2.1 (17) | −34.2 ± 0.5 (17) | 6.6 ± 0.2 (17) | −73.3 ± 0.8 (17) #### | 4.6 ± 0.1 (17) | 3.2 ± 0.2 (15) | 52.7 ± 8.6 (15) |
| iFGF13 shRNA + iFGF13-VY-230-232A | −44.1 ± 4.8 (19) | 0.78 ± 0.04 (19) | 0.83 ± 0.03 (16) | 4.6 ± 0.3 (16) | 22.2 ± 2.9 (16) | −35.4 ± 0.8 (19) | 7.7 ± 0.2 (19) | −76.8 ± 1.0 (16) #### | 4.8 ± 0.2 (16) | 3.1 ± 0.2 (14) | 59.3 ± 10.5 (14) |
| iFGF13 shRNA + iFGF13-VY-230-232E | −55.9 ± 6.1 (20) | 0.74 ± 0.03 (20) | 0.75 ± 0.02 (19) *** | 3.8 ± 0.2 (19) | 21.4 ± 2.9 (19) # | −36.4 ± 0.6 (20) ** | 6.7 ± 0.2 (20) | −74.8 ± 0.6 (18) #### | 4.4 ± 0.1 (18) | 2.4 ± 0.2 (19) | 55.1 ± 4.8 (19) |
| iFGF13 shRNA + iFGF13-VY-238-240A | −58.1 ± 4.9 (26) | 0.73 ± 0.02 (24) | 0.77 ± 0.03 (23) ** | 4.2 ± 0.3 (23) | 18.8 ± 1.9 (23) | −36.9 ± 0.7 (24) *** | 7.2 ± 0.2 (24) | −77.8 ± 0.9 (20) ### | 4.5 ± 0.1 (20) | 2.8 ± 0.1 (18) | 64.6 ± 5.0 (18) |
| iFGF13 shRNA + iFGF13-VY-238-240E | −58.3 ± 6.6 (22) | 0.77 ± 0.02 (20) | 0.82 ± 0.03 (16) | 4.6 ± 0.4 (16) | 17.2 ± 1.8 (16) # | −33.7 ± 0.5 (20) | 7.3 ± 0.1 (20) | −76.1 ± 1.0 (17) #### | 4.4 ± 0.1 (17) | 2.5 ± 0.2 (12) | 64.1 ± 13.2 (12) |
| iFGF13 shRNA + iFGF13-VY-250-255A | −71.8 ± 7.0 (16) | 0.75 ± 0.03 (16) | 0.73 ± 0.02 (16) *** | 3.9 ± 0.3 (16) | 15.8 ± 1.4 (16) # | −36.4 ± 0.7 (16) ** | 6.9 ± 0.2 (16) | −75.0 ± 1.0 (14) #### | 4.9 ± 0.2 (14) | 2.4 ± 0.1 (14) | 65.3 ± 7.1 (14) |
| iFGF13 shRNA + iFGF13-VY-250-255E | −52.4 ± 7.0 (19) | 0.79 ± 0.02 (17) | 0.82 ± 0.04 (17) | 5.0 ± 0.3 (17) | 19.6 ± 1.8 (17) | −34.0 ± 0.9 (17) | 7.4 ± 0.2 (17) | −75.0 ± 1.0 (15) #### | 4.6 ± 0.2 (15) | 2.6 ± 0.1 (15) | 49.4 ± 5.5 (15) |
| iFGF13 shRNA + iFGF13-VY-9A | −64.1 ± 7.7 (15) | 0.75 ± 0.02 (15) | 0.75 ± 0.03 (13) ** | 3.3 ± 0.1 (13) | 12.7 ± 1.8 (13) ### | −36.2 ± 0.8 (15) * | 7.2 ± 0.3 (15) | −77.4 ± 0.6 (10) ## | 4.2 ± 0.1 (10) | 4.4 ± 0.4 (8) | 78.5 ± 7.6 (8) |
Whole-cell voltage-gated Na+ currents were recorded 48 h following infection of neonatal WT mouse ventricular cardiomyocytes with adenoviruses expressing control shRNA, iFGF13 shRNA alone, or with WT (iFGF13-VY-WT), phosphosilent (mutation to alanine), or phosphomimetic (mutation to glutamate) iFGF13-VY cDNA constructs using the protocols described in the Materials and methods section. The peak Na+ current (INa) density, time to peak INa, and time course of inactivation properties presented were determined from analyses of records obtained on depolarizations to −10 mV (HP = −120 mV). All values are means ± SEM. The number of cells analyzed is provided in parentheses. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 versus control shRNA; #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001 versus iFGF13 shRNA; one-way ANOVA.