The Journal of Neuroscience, July 1, 2000, 20(13):4786-4797
Sustained Activation of Hippocampal Lp-Type Voltage-Gated Calcium
Channels by Tetanic Stimulation
Jessica M.
Schjött and
Mark R.
Plummer
Rutgers University, Department of Cell Biology and Neuroscience,
Nelson Laboratories, Piscataway, New Jersey 08854-8082
The molecular heterogeneity of voltage-gated calcium channels is
mirrored by extensive biophysical diversity. Subtype-selective antagonists have been used to place different kinds of calcium channels
in functional categories. Dihydropyridine (DHP) antagonists have been
used, for example, to implicate L-type calcium channels in the
induction of NMDA receptor-independent forms of synaptic plasticity.
DHPs, however, do not discriminate between the recently identified Lp
and Ls subtypes of L-type calcium channel. The different properties of
the two kinds of L-type channels suggest that they may have different
functional roles. Ls channels are comparable with cardiac L-type
channels, whereas Lp channels show low-threshold voltage-dependent
potentiation. To clarify the potential roles of Lp and Ls channels in
the induction of synaptic plasticity, we studied the responses of these
channels to trains of action potentials. The frequency and duration of
the trains were chosen to mimic the stimuli used to induce changes in
synaptic strength. Cell-attached single-channel recordings from
cultured hippocampal neurons revealed that both Lp and Ls channels
responded to these trains, but only Lp channels showed persistent
activation that outlasted the train. The magnitude of Lp channel
activity increased with increasing action potential frequency and train
duration. Stimuli that reproduced the postsynaptic response to action
potential trains were also examined, and Lp channels were found to show much greater responses than were Ls channels. These results suggest that the Lp channel may play a critical role in the induction of
long-lasting changes in synaptic strength.
Key words:
calcium channel; hippocampus; potentiation; long-term
potentiation; synaptic plasticity; dihydropyridine; L-type
Copyright © 2000 Society for Neuroscience 0270-6474/00/20134786-12$05.00/0