Phosphorylation of HERG channels by PKC and PKA affect protein abundance. A, inhibition of PKC (with Bis-I) reduces the α1A-AR-mediated increase in HERG more than inhibition of PKA (with H-89), and inhibition of both kinases completely prevents the effect; ∗, p < 0.05, n = 5. B, representative current traces from HEK cells expressing either HERGΔPKC (left) or HERGΔPKA (right). C, immunoblot of HERG, HERGΔPKC, and HERGΔPKA before and after treatment of cells with either PMA or CPT-cAMP. D, summary densitometry data from HERG immunoblot analysis shown in C (∗, significance compared with CPT-cAMP-treated cells, p < 0.05, n = 2). The effects of PKA and PKC stimulation on HERG abundance are partially cumulative. Direct phosphorylation of the channel protein largely accounts for the kinase effects on HERG.