Parkinson's disease: return of an old prime suspect.
Pacemaking activity in adult substantia nigra (SN) dopamine neurons relies on L-type Ca2+ channels, but a surprising study in Nature by Chan et al. demonstrates that blockade of these channels by dihydropyridines re-establishes the pacemaking driven by sodium and HCN channels found in juvenile SN. This shift protects SN neurons in chemical models of Parkinson's disease (PD), suggesting that elevated intracellular Ca2+ participates in SN cell loss and that dihydropyridines may provide therapy in PD.
Sulzer
David
D
Department of Neurology, Columbia University Medical School, New York State Psychiatric Institute, New York, NY 10032, USA. ds43@columbia.edu
Schmitz
Yvonne
Y
D000818:Animals; D000978:Antiparkinson Agents; D001683:Biological Clocks / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D054815:Cyclic Nucleotide-Gated Cation Channels; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D010300:Parkinson Disease / Q000235:genetics / Q000503:physiopathology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology*
D000978:Antiparkinson Agents; D020746:Calcium Channels, L-Type; D054815:Cyclic Nucleotide-Gated Cation Channels; D004095:Dihydropyridines; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels