Multiple calcium channels mediate neurotransmitter release from peripheral neurons

We examined the effects of dihydropyridine drugs on evoked neurotransmitter release from cultured neonatal rat sensory and sympathetic neurons. Depolarization with K⁺-rich solutions increased the release of substance P from cultured sensory neurons. This release was enhanced by BAY K8644 and (+)-202791 and was blocked by a variety of other dihydropyridines including (-)-202791, by Co²⁺, or in Ca²⁺-free solutions. K⁺-rich solutions also stimulated the release of [³H]norepinephrine from cultured sympathetic neurons. This release was also completely blocked by Co²⁺ or in Ca²⁺-free solution. In contrast to the situation in sensory neurons, however, the evoked release of [³H]norepinephrine was completely resistant to the blocking effects of dihydropyridine such as nimodipine. However, BAY K8644 was able to enhance the evoked release of [³H]norepinephrine, and this enhancement was blocked by nimodipine. These results are discussed in relation to the possible participation of multiple types of calcium channels in the release of neurotransmitters.