DIHYDROPYRIDINE-SENSITIVE, VOLTAGE-GATED CA2+ CHANNELS CONTRIBUTE TO THE RESTING INTRACELLULAR CA2+ CONCENTRATION OF HIPPOCAMPAL CA1 PYRAMIDAL NEURONS

1. Whole cell recordings and high-speed fluorescence imaging were used to investigate the contribution of voltage-gated Ca2+ channels to the resting Ca2+ concentration ([Ca2+](i)) in hippocampal CAl pyramidal n eurons. 2. Prolonged membrane hyperpolarization produced, in a volt ag e-dependent manner, sustained decreases in [Ca2+](i) in the somatic an d apical dendritic regions of the neuron. This hyperpolarization-induc ed decrease in [Ca2+](i) occurred with a time constant of similar to 1 s and was maintained for as long as the membrane potential was held a t the new level. Ratiometric measures showed that [Ca2+](i) is signifi cantly elevated at holding potentials of -50 mV compared with -80 mV. 3. The hyperpolarization-induced decrease in [Ca2+](i) was reduced sig nificantly by 200 mu M Cd2+ and 10 mu M nimodipine, bur was only sligh tly inhibited by 50 mu M Ni2+. The largest amplitude decrease in [Ca2](i) was observed in the proximal apical dendrites with the amplitude of the Ca2+ change decreasing with further distance from the soma. 4. Whole cell recordings from acutely isolated hippocampal pyramidal neur ons reveal a slowly inactivating Ca2+ current with similar voltage dep endence and pharmacology to the hyperpolarization-induced decrease in [Ca2+](i). 5. The data suggest that a population of dihydropyridine-se nsitive Ca2+ channels are active at resting membrane potentials and th at this channel activation significantly contributes to the resting [C a2+](i), These channels appear to be present throughout the neuron and may be located most densely in the proximal apical dendrites.