Figure 1. Mechanisms that regulate K_V1.5 channel trafficking in arterial smooth muscle cells.

K_V1.5 continuously recycles between the cytosol and plasma membrane. Intravascular pressure stimulates arterial smooth muscle cell membrane depolarization, leading to Ca_V1.2 channel activation. The increase in [Ca²⁺]_i inhibits K_V1.5 channel degradation, allowing K_V1.5 to recycle to the plasma membrane. A reduction in intravascular pressure leads to membrane hyperpolarization which promotes the degradation of K_V1.5 protein through a process that involves both proteasomes and lysosomes. Angiotensin II binding to a surface receptor (ATIIR) activates protein kinase C, which stimulates the degradation of internalized K_V1.5 channels, leading to a reduction in the amount of protein that is returned to the surface. Through this mechanism angiotensin II reduces surface K_V1.5 protein, which decreases K_V1.5 current density, leading to vasoconstriction. Green and red arrows indicate activation and inhibition, respectively.