Intracellular calcium store filling by an L-type calcium current in the basolateral amygdala at subthreshold membrane potentials

The long-term changes that underlie learning and memory are activated by rises in intracellular Ca²⁺ that activate a number of signalling pathways and trigger changes in gene transcription. Ca²⁺ rises due to influx via L-type voltage-dependent Ca²⁺ channels (L-VDCCs) and release from intracellular Ca²⁺ stores have been consistently implicated in the biochemical cascades that underlie the final changes in memory formation. Here, we show that pyramidal neurones in the basolateral amygdala express an L-VDCC that is active at resting membrane potentials. Subthreshold depolarization of neurones either by current injection or summating synaptic potentials led to a sustained rise in cytosolic Ca²⁺ that was blocked by the dihydropyridine nicardipine. Activation of metabotropic receptors released Ca²⁺ from intracellular Ca²⁺ stores. At hyperpolarized potentials, metabotropic-evoked store release ran down with repeated stimulation. Depolarization of cells to - 50 mV, or maintaining them at the resting membrane potential, restored release from intracellular Ca²⁺ stores, an effect that was blocked by nicardipine. These results show that Ca²⁺ influx via a low-voltage-activated L-type Ca²⁺ current refills inositol 1,4,5-trisphosphate (IP₃)-sensitive intracellular Ca²⁺ stores, and maintains Ca²⁺ release and wave generation by metabotropic receptor activation.