The goal of these studies was to determine if different calcium channel antagonists affect glucose transport in a neuronal cell line. Rat pheochromocytoma (PC12) cells were treated with L-, T- and N-type calcium channel antagonists prior to measuring the accumulation of ³H-2-deoxyglucose (³H-2-DOG). The L-type channel antagonists, nimodipine, nifedipine, verapamil, and diltiazem all inhibited glucose transport in a dose-dependent manner (2 to 150 µM) with nimodipine being the most potent and diltiazem only moderately inhibiting transport. Antagonists of T- and N-type calcium channels had no effect on transport. The L-type channel agonist (-) Bay K 8644 also inhibited the uptake of ³H-2-DOG. The ability of these drugs to inhibit glucose transport was significantly diminished by the presence of unlabeled 2-deoxyglucose in the uptake medium. Some experiments were performed in the presence of EDTA or in uptake buffer without calcium. The absence of calcium in the uptake medium had no effect on the inhibition of glucose transport by nimodipine or verapamil. To examine the effects of these drugs on a cell model of a peripheral tissue, rat L6 muscle cells were studied. The drugs inhibited glucose transport in L6 cells in a dose-dependent manner that was independent of calcium in the uptake medium. These studies suggest that the calcium channel antagonists can inhibit glucose transport in cells through mechanisms other than the antagonism of calcium channels, perhaps by acting directly on GLUTs