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 neurons. 2. Prolonged membrane hyperpolarization produced, in a volt age-dependent manner, sustained decreases in [Ca2+](i) in the somatic and apical dendritic regions of the neuron. This hyperpolarization-induced 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 at the new level. Ratiometric measures showed that [Ca2+](i) is significantly elevated at holding potentials of -50 mV compared with -80 mV. 3. The hyperpolarization-induced decrease in [Ca2+](i) was reduced significantly by 200 mu M Cd2+ and 10 mu M nimodipine, bur was only slightly 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 neurons reveal a slowly inactivating Ca2+ current with similar voltage dependence and pharmacology to the hyperpolarization-induced decrease in [Ca2+](i). 5. The data suggest that a population of dihydropyridine-sensitive Ca2+ channels are active at resting membrane potentials and that this channel activation significantly contributes to the resting [Ca2+](i), These channels appear to be present throughout the neuron and may be located most densely in the proximal apical dendrites.