Figure 7. A basic model of activity-dependent, steady-state regulation of functional VGSC expression in Mat-LyLu cells by positive feedback (continuous lines).

Influx of Na⁺ through VGSCs results in activation of AC and PKA. PKA can have multiple effects on VGSC expression in plasma membrane (PM): (1) potentiation of de novo VGSC synthesis via transcription; and (2) increased trafficking of VGSC protein to the plasma membrane. In addition, PKA can directly phosphorylate surface-expressed VGSCs (dashed line), although this may be independent of Na⁺.