Voltage-gated calcium channels provide an alternate route for iron uptake in neuronal cell cultures.
Recent studies suggest that iron enters cardiomyocytes via the L-type voltage-gated calcium channel (VGCC). The neuronal VGCC may also provide iron entry. As with calcium, extraneous iron is associated with the pathology and progression of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. VGCCs, ubiquitously expressed, may be an important route of excessive entry for both iron and calcium, contributing to cell toxicity or death. We evaluated the uptake of (45)Ca(2+) and (55)Fe(2+) into NGF-treated rat PC12, and murine N-2alpha cells. Iron not only competed with calcium for entry into these cells, but iron uptake (similar to calcium uptake) was inhibited by nimodipine, a specific L-type VGCC blocker, and enhanced by FPL 64176, an L-VGCC activator, in a dose-dependent manner. Taken together, these data suggest that voltage-gated calcium channels are an alternate route for iron entry into neuronal cells under conditions that promote cellular iron overload toxicity.
Gaasch
Julie A
JA
Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Texas 79106, USA.
Geldenhuys
Werner J
WJ
Lockman
Paul R
PR
Allen
David D
DD
Van der Schyf
Cornelis J
CJ
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000502:physiology; D007501:Iron / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology; D016716:PC12 Cells; D010641:Phenotype; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D011758:Pyrroles; C071658:FPL 64176; D009553:Nimodipine; D007501:Iron; D002118:Calcium