Fig. 5.

CaMKII and PKC mediate the hyperglycemia effects on K⁺ channels. a Schematic of potential protein kinase pathways that may mediate the hyperglycemia effects on K⁺ channels and their selective inhibitors. b–f Inhibition of CaMKII using the specific autocamp-tide-2 related inhibitory peptide (AIP, 1 μmol/L) prevented the hyperglycemia effects on I_K1 (b, c) and I_to recovery (e, f) in mouse ventricular myocytes. Selective inhibition of protein kinase C (PKC) using bisindolylmaleimide II (BIM-II, 100 nmol/L) prevented I_to reduction in hyperglycemia (d). Protein kinase A (PKA) inhibition using the selective protein kinase inhibitory peptide (PKI, 1 μmol/L) had no effect on K⁺ channels in hyperglycemia. g Schematic of PKC isoforms and inhibitors. h Go 6976 (100 nmol/L), a selective inhibitor of conventional, Ca²⁺-dependent PKC isoforms (PKCα and β) prevented I_to reduction in hyperglycemia. BIM-V (100 nmol/L), a structurally related but inactive analogue of PKC inhibitors had no effect on I_to in normal glucose and did not prevent I_to reduction in hyperglycemia. i I-V relationship of I_to following Go 6976 and BIM-V pretreatments. Two-way ANOVA; *p < 0.05, **p < 0.01, ***p < 0.001 vs. normoglycemia; ^†p < 0.05 vs. control