Graded action potentials generated by differentiated human neuroblastoma cells.
Stimulus-dependent impulses and resting membrane parameters of human SH-SY5Y neuroblastoma cells, induced to differentiate by retinoic acid, were investigated with tight-seal recording techniques. Mean resting potential was -53 mV, mean input resistance 2.1 G omega, mean capacitance 14 pF, and mean time constant 30 ms. Rectangular current steps induced clearly stimulus-dependent impulses, with stronger current steps causing impulses of larger amplitude. The degree of impulse variability differed significantly among different cells. The current thresholds for impulse generation ranged from 35 to 100 pA for 10 ms current steps. With longer current steps, thresholds below 10 pA were recorded. In response to 0.5-1 s long current steps, most cells generated only a single impulse, but a few cells generated two impulses. When two impulses were generated, the interval between the impulses decreased with increasing stimulus strength. Whole-cell currents were recorded under voltage-clamp conditions. Voltage-activated, tetrodotoxin-sensitive Na+ currents and 'delayed rectifier' K+ currents were recorded. The degree of impulse variability was correlated to the maximum Na+ current density. Cells with large Na+ currents showed little impulse variability, while a marked variability was recorded in cells with intermediate or small Na+ currents. Cells which generated more than one impulse in response to prolonged stimuli belonged to the group with large Na+ currents. Spontaneous impulse-currents were recorded from cell-attached membrane patches on intact cells. Also these impulses showed a large variability in amplitude: In each of five cells analysed, the peak-to-peak amplitude varied by a factor larger than 1.7.
Department of Neurochemistry and Neurotoxicology, Stockholm University, Sweden.
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Johansson
D000200:Action Potentials / Q000502:physiology; D001932:Brain Neoplasms / Q000503:physiopathology*; D004594:Electrophysiology; D006801:Humans; D009447:Neuroblastoma / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015222:Sodium Channels; D013779:Tetrodotoxin