Chronic reduction in complex I function alters calcium signaling in SH-SY5Y neuroblastoma cells

Sporadic, non-familial Parkinson's disease is characterized by a 15-30% red uction in complex I activity of the electron transport chain. A pharmacolog ical model of reduced complex I activity was created by prolonged treatment of SH-SY5Y cells with low doses (5-20 nM) of rotenone, a selective inhibit or of complex I. Short-term (less than 2 week) exposure to rotenone did not influence calcium signaling, production of reactive oxygen species, or mit ochondrial morphology. However, following 2 weeks of rotenone exposure, SH- SY5Y cells showed unusual calcium dynamics, specifically multiple calcium r esponses to carbachol, a muscarinic agonist. These secondary calcium respon ses were not seen in control SH-SY5Y cells and were dependent upon calcium influx. Mitochondrial membrane potential was also reduced in low dose roten one-treated cells. These results demonstrate that a chronic, partial reduct ion in complex I activity, such as that seen in Parkinson's disease, can al ter cell signaling events and perhaps increase the susceptibility of cells to calcium overload and subsequent cell death. (C) 2001 Elsevier Science BN . All rights reserved.