MULTIPLE VOLTAGE-DEPENDENT MECHANISMS POTENTIATE CALCIUM-CHANNEL ACTIVITY IN HIPPOCAMPAL-NEURONS

Neuronal voltage-gated calcium channels provide a pathway for calcium influx that is required for processes ranging from intracellular signa ling to alterations in cellular excitability. In hippocampal neurons, we have characterized a subtype of dihydropyridine-sensitive L-type ca lcium channels (Lp channel) that shows multiple kinds of voltage-depen dent potentiation of its activity. One type of potentiation is elicite d by low-voltage stimuli (-10 mV) and can be seen in dual-pulse protoc ols in which a transient hyperpolarization is interposed between condi tioning and test pulses. The second type of potentiation is elicited b y much higher voltages (+60 mV) and is selectively deactivated at hype rpolarized voltages. We have compared these types of potentiation in t he Lp channel, the ''standard'' L-type channel, and the cardiac L-type channel. Our results show that the high-voltage potentiation is commo n to all three channel types. The low-voltage form of potentiation, ho wever, is unique to the Lp channel. Thus, the Lp channel shows two kin ds of potentiation that differ in their voltage dependence and rate of decay. Therefore, calcium channel plasticity in the hippocampus has a variety of forms distinguished by their stimulus requirements and dur ation.