Sustained activation of hippocampal Lp-type voltage-gated calcium channels by tetanic stimulation

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.