1 Calcium - independent inhibition of glucose transport in PC 12 and L 6 cells by calcium channel antagonists

The goal of these studies was to determine if different calcium channel antagonists affect glucose transport in a neuronal cell line. For these studies, rat pheochromocytoma (PC12) cells were treated with L-, Tand N-type calcium channel antagonists prior to measuring the accumulation of H-2-deoxyglucose (H-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 Tand N-type calcium channels had no effect on transport. The L-type channel agonist (-) Bay K 8644 also inhibited the uptake of H-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 (4 mM) 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 myoblasts in a dosedependent manner that was independent of calcium in the uptake medium. These studies suggest that the calcium channel antagonists inhibit glucose transport in cells through mechanisms other than the antagonism of calcium channels, perhaps by acting directly on glucose transporters (GLUTs).