Late Na<sup>+</sup> Current Is [Ca<sup>2+</sup>]<sub>i</sub>-Dependent in Canine Ventricular Myocytes
Enhancement of the late sodium current (I<sub>NaL</sub>) increases arrhythmia propensity in the heart, whereas suppression of the current is antiarrhythmic. In the present study, we investigated I<sub>NaL</sub> in canine ventricular cardiomyocytes under action potential volta...
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| Autores principales: | , , , , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/cedd9842b323421d81788f7c883d48be |
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| Sumario: | Enhancement of the late sodium current (I<sub>NaL</sub>) increases arrhythmia propensity in the heart, whereas suppression of the current is antiarrhythmic. In the present study, we investigated I<sub>NaL</sub> in canine ventricular cardiomyocytes under action potential voltage-clamp conditions using the selective Na<sup>+</sup> channel inhibitors GS967 and tetrodotoxin. Both 1 µM GS967 and 10 µM tetrodotoxin dissected largely similar inward currents. The amplitude and integral of the GS967-sensitive current was significantly smaller after the reduction of intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) either by superfusion of the cells with 1 µM nisoldipine or by intracellular application of 10 mM BAPTA. Inhibiting calcium/calmodulin-dependent protein kinase II (CaMKII) by KN-93 or the autocamtide-2-related inhibitor peptide similarly reduced the amplitude and integral of I<sub>NaL</sub>. Action potential duration was shortened in a reverse rate-dependent manner and the plateau potential was depressed by GS967. This GS967-induced depression of plateau was reduced by pretreatment of the cells with BAPTA-AM. We conclude that (1) I<sub>NaL</sub> depends on the magnitude of [Ca<sup>2+</sup>]<sub>i</sub> in canine ventricular cells, (2) this [Ca<sup>2+</sup>]<sub>i</sub>-dependence of I<sub>NaL</sub> is mediated by the Ca<sup>2+</sup>-dependent activation of CaMKII, and (3) I<sub>NaL</sub> is augmented by the baseline CaMKII activity. |
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