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

The molecular heterogeneity of voltage-gated calcium channels is mirrored b y 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 implicat e L-type calcium channels in the induction of NMDA receptor-independent for ms of synaptic plasticity. DHPs, however, do not discriminate between the r ecently identified Lp and Ls subtypes of L-type calcium channel. The differ ent properties of the two kinds of L-type channels suggest that they may ha ve different functional roles. Ls channels are comparable with cardiac L-ty pe channels, whereas Lp channels show low-threshold voltage-dependent poten tiation. To clarify the potential roles of Lp and Ls channels in the induct ion of synaptic plasticity, we studied the responses of these channels to t rains of action potentials. The frequency and duration of the trains were c hosen to mimic the stimuli used to induce changes in synaptic strength. Cel l-attached single-channel recordings from cultured hippocampal neurons reve aled that both Lp and Ls channels responded to these trains, but only Lp ch annels showed persistent activation that outlasted the train. The magnitude of Lp channel activity increased with increasing action potential frequenc y and train duration. Stimuli that reproduced the postsynaptic response to action potential trains were also examined, and Lp channels were found to s how much greater responses than were Ls channels. These results suggest tha t the Lp channel may play a critical role in the induction of long-lasting changes in synaptic strength.