Enhanced L-type Ca²⁺ channel (LTCC) activity in arterial myocytes contributes to vascular dysfunction during diabetes. Modulation of LTCC activity under hyperglycemic conditions could result from membrane potential-dependent and independent mechanisms. We have demonstrated that elevations in extracellular glucose (HG), similar to hyperglycemic conditions during diabetes, stimulate LTCC activity through phosphorylation of Ca_V1.2 at serine 1928. Prior studies have also shown that HG can suppress the activity of K⁺ channels in arterial myocytes, which may contribute to vasoconstriction via membrane depolarization. Here, we used a mathematical model of membrane and Ca²⁺ dynamics in arterial myocytes to predict the relative roles of LTCC and K⁺ channel activity in modulating global Ca²⁺ in response to HG. Our data revealed that abolishing LTCC potentiation normalizes [Ca²⁺]_i, despite the concomitant reduction in K⁺ currents in response to HG. These results suggest that LTCC stimulation may be the primary mechanism underlying vasoconstriction during hyperglycemia.