The biochemistry of the neuron. Neurosecretory habituation to repetitive depolarizations in PC12 cells.

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.