Abstract
Using video-enhanced microscopy, we found that 4-aminopyridine (4-AP), known as a membrane permeable blocker of K+ channels, induced Brownian movement of organelles within 5 min in cultured dorsal root ganglion (DRG) neurons and non-neuronal cells. The Brownian movement gradually became rapid, and then organelles excavated the surrounding cytoplasm and formed vacuoles. Intracellular actin filaments were pushed away from the vacuoles but microtubules were not significantly affected. These phenomena were reversed by washout after 1-hour treatment of 4-AP, but longer treatment (4-24 hours) resulted in cell death. Other aminopyridines, 2-AP, 3-AP and 3,4-diamynopyridine, also evoked Brownian movement of organelles and formed vacuoles, but other K+ channel blockers tetraethylammonium (TEA), Cs+ and apamin had no effect. The observed effects of 4-AP were prevented by elimination of intracellular Cl− from extracellular medium and by the vacuolar H+ ATPase inhibitor bafilomycin A1. These results suggest that intracellular 4-AP and Cl− may be coupled to activation of vacuolar H+ ATPase to cause Brownian movement of organelles. Aminopyridines therefore possess a unique effect on organelle movement and cytoplasm, which are associated with changes in the cytoskeleton organization and cell death. [Jpn J Physiol 54 Suppl:S78 (2004)]
