TABLE 3.
Proteins and their modulation effects on the gating properties of NaV1.5 channels.
| Proteins | Interacting domains | Modulation effects of gating properties | References | |
| β-subunits | β1 | DIV-VSD | Co-expression of β1 with cardiac NaV1.5 in Xenopus oocytes increased INa amplitude, resulting in a depolarizing shift in steady-state inactivation and enhances recovery from inactivation. Overexpressing β1 caused significant hyperpolarizing shifts in both activation and inactivation kinetics, and greatly reduced persistent INa–L in the Chinese hamster ovary cells stably expressing human NaV1.5. | Fahmi et al., 2001; Ko et al., 2005; Zhu et al., 2017 |
| β2 | Co-expression of β2 with NaV1.5 caused a negative shift in activation in Pro5 and Lec2 cells. Co-expression of β2 with NaV1.5 caused a positive shift in inactivation in Chinese hamster ovary cells. | Johnson and Bennett, 2006; Watanabe et al., 2009 | ||
| β3 | DIII-VSD | Overexpressing β3 accelerated macroscopic current decay, caused hyperpolarizing shifts in both activation and inactivation kinetics, slowed recovery from inactivation, and greatly reduced persistent INa–L in the Chinese hamster ovary cells stably expressing human NaV1.5. | Ko et al., 2005; Zhu et al., 2017 | |
| β4 | Controversial. Medeiros-Domingo’s study showed that overexpression of β4 with NaV1.5 significantly increased the slope factors of both activation and inactivation, shifted the inactivation curve to a more negative potential, and reduced slow recovery from inactivation in HEK293 cells stably expressing NaV1.5. Tan’s study showed that co-expression of β4 with NaV1.5 did not affect the activation or recovery from inactivation of the cardiac sodium current, but significantly shifted the inactivation curve to a more negative potential in HEK293 cells. However, in Qin Yang’s study, they did not observe any significant effect. | Medeiros-Domingo et al., 2007; Tan et al., 2010; Yang et al., 2019 | ||
| FGF | FGF12 | C-terminus | Overexpression of FGF12 exhibited a significant hyperpolarizing shift in voltage-dependent inactivation without affecting the activation of NaV1.5. | Liu et al., 2003 |
| FGF13 | C-terminus | The knockout of FGF13 in adult mouse ventricular myocytes delayed recovery from inactivation of NaV1.5. | Wang et al., 2011 | |
| CaMKII | IQ motif | Overexpressing CaMKII exhibited a depolarizing shift in sodium channel inactivation and increased INa–L in rabbit, mouse and the guinea pig ventricular cardiomyocytes. Its effects on recovery from inactivation and intermediate or slow inactivation of NaV1.5 are controversial. | Aiba et al., 2010; Wagner et al., 2006 | |
| 14-3-3η | the first interdomain of NaV1.5 between amino acids 417 and 467 | The co-expression of NaV1.5, β1 subunit and 14-3-3η in the COS-7 cells resulted in a negative shift in inactivation and a delayed recovery from inactivation without changes in the activation and current density. 14-3-3η mediated coupled gating. | Allouis et al., 2006; Clatot et al., 2017 | |