Abstract
Habituation in response to repetitive depolarization of PC12 cells can be used as a model for memory processes at the molecular level. In response to depolarization by high external potassium, a triphasic elevation in internal calcium levels occurred. Calcium elevation was maximal immediately after addition of the stimulus (phase 1), followed by a 2-min period in which the calcium level decreased (phase 2), leading to a new steady-state level which was higher than in the unstimulated cell (phase 3). In response to repetitive depolarizations, the calcium level in phase 1 was reduced by as much as 43%, and phase 3 was reduced by as much as 40%. By measuring the relationship between calcium elevation and secretion, it was shown that measured reductions in calcium levels were correlated with neurosecretory habituation. One of the components responsible for the reductions in calcium levels was a tetraethylammonium-sensitive potassium channel, and the habituation of this channel was reversed by addition of 4 beta-phorbol 12-myristate 13-acetate.
Highlights
Habituation in response to repetitive depolarization of PC12 cells can be used as a model for memory processes at the molecular level
We have demonstrated that calcium levels become habituated in response to repetitive depolarizatiobnys high potassium
The calcium level immediately after high K+ stimulationwas reducedby as much a4s3%and theelevated steady-state calcium level in cells stimulated for several minutes was reduced by as much as40% in response to level of secretion was increased, as with the Tetraethylammonium chloride (TEA) experimentr.epetitive stimulations withhigh K+
Summary
Habituation in response to repetitive depolarization of PC12 cells can be used as a model for memory processes at the molecular level. In response to depolarization by high external potassium, a triphasic elevation in internal calcium levels occurred. In response to repetitive depolarizations, the calcium level in phase 1 was reduced byas much as 43%a, nd phase 3 was reduced by as much as 40%. Oneof the components responsible for the reductions in calcium levels wasa tetraethylammonium-sensitive potassium channel, and the habituation of this channel was reversed by addition of 4&phorbol 12-myristate 13-acetate. Rosecretory habituation can occur in single mammalian cells. As calcium entry is required for secretion to occur [16], we have investigated the role of calcium in the mechanismof secretory habituation in PC12 cells
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