Figure 2: The modulation of HCN channels by 5-HT and related intracellular signal pathways. 5-HT binds to specific G-coupled receptors and modulates the activity of HCN channels via the PLC-PKC or p38-MAPK signaling pathways. Activation of PKC suppresses the activation of HCN channels and diminishes HCN surface expression, whereas p38-MAPK causes a positive shift of HCN channels voltage-dependent activation.