Nimodipine decreases calcium action potentials in rabbit hippocampal CA1 neurons in an age-dependent and concentration-dependent manner.
Intracellular recordings were made from rabbit hippocampal CA1 neurons in vitro using slices from aging and young adult rabbits. Calcium action potentials were studied in the presence of 4 microns tetrodotoxin using electrodes filled with 2M CsCl. Increasing concentrations of the dihydropyridine L-type calcium channel antagonist nimodipine were tested on the amplitude and time course of calcium action potentials. The calcium action potential (AP) consisted of two components: an initial fast phase followed by a slower plateau phase. No difference in the peak amplitude of the initial fast phase was observed between age groups. The amplitude and duration of the slower plateau phase of the calcium AP was significantly larger in aging neurons. Switching to a zero Ca2+ medium in the presence of 200 microns CdCl2 completely blocked the calcium AP. Nimodipine decreased the plateau phase of the calcium AP at concentrations as low as 100 nm in aging neurons and 10 microns in young neurons. Switching to higher concentrations of nimodipine did not reveal any substantially increased block of the calcium AP plateau phase. These data suggest that enhanced calcium influx through L-type calcium channels is largely responsible for the enhanced calcium action potentials observed in aging CA1 neurons. The action of nimodipine in reducing the plateau phase of the calcium action potential may underlie the drug's notable ability to improve learning in hippocampally dependent tasks in aging animals.
Moyer
J R
JR
Department of Cell, Molecular, and Structural Biology, Northwestern University Medical School, Chicago, Illinois 60611-3008.
Disterhoft
J F
JF
D000200:Action Potentials / Q000187:drug effects*; D000375:Aging / Q000502:physiology*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D019256:Cadmium Chloride; D002118:Calcium / Q000037:antagonists & inhibitors*; D015220:Calcium Channels / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009553:Nimodipine / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D013779:Tetrodotoxin / Q000494:pharmacology
D015220:Calcium Channels; D002712:Chlorides; D002104:Cadmium; D013779:Tetrodotoxin; D009553:Nimodipine; D019256:Cadmium Chloride; D002118:Calcium