Differential contribution of L- and N-type calcium channels on rat hippocampal acetylcholine release

Bay K 8644, nimodipine and omega-conotoxin GVIA (omega-CgTx) were used to study the different contribution of voltage-sensitive calcium channels (VSCC) to [3H]acetylcholine ([[3H]ACh) release in rat hippocampal synaptosomes. In our experimental conditions, the percentage of calcium-dependent ACh release was approximately 80%. Nimodipine (0.01-10 microM) and Bay 8644 (0.01-10 microM) were not able to modify the [3H]ACh release under stimulating conditions (15 mM K+). Nevertheless, when K+ concentration was reduced to 8 mM, a significant increase in [3H]ACh release was observed at 1 and 10 microM of Bay K 8644. Nimodipine (0.01-10 microM) failed to reverse the effect of Bay K 8644 on [3H]ACh release. Finally, omega-CgTx (0.001-1 microM) caused a concentration-dependent reduction of [3H]ACh release in K+ (15 mM)-stimulating conditions. These results suggest that the N-type VSCC probably play a predominant role in regulating the [3H]ACh release in synaptosomes from rat hippocampus.