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 CA1 pyramidal neurons. 2. Prolonged membrane hyperpolarization produced, in a voltage-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 approximately 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 microM Cd2+ and 10 microM nimodipine, but was only slightly inhibited by 50 microM 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.
Magee
J C
JC
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
Avery
R B
RB
Christie
B R
BR
Johnston
D
D
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D009553:Nimodipine / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D009553:Nimodipine; C038806:1,4-dihydropyridine; D002118:Calcium