Turner T J, Adams M E, Dunlap K
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111.
Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9518-22. doi: 10.1073/pnas.90.20.9518.
The regulation of excitation-secretion coupling by Ca2+ channels is a fundamental property of the nerve terminal. Peptide toxins that block specific Ca2+ channel types have been used to identify which channels participate in neurotransmitter release. Subsecond measurements of [3H]-glutamate and [3H]dopamine release from rat striatal synaptosomes showed that P-type channels, which are sensitive to the Agelenopsis aperta venom peptide omega-Aga-IVA, trigger the release of both transmitters. Dopamine (but not glutamate) release was also controlled by N-type, omega-conotoxin-sensitive channels. With strong depolarizations, where neither toxin was very effective alone, a combination of omega-Aga-IVA and omega-conotoxin produced a synergistic inhibition of 60-80% of Ca(2+)-dependent dopamine release. The results suggest that multiple Ca2+ channel types coexist to regulate neurosecretion under normal physiological conditions in the majority of nerve terminals. P- and N-type channels coexist in dopaminergic terminals, while P-type and a omega-conotoxin- and omega-Aga-IVA-resistant channel coexist in glutamatergic terminals. Such an arrangement could lend a high degree of flexibility in the regulation of transmitter release under diverse conditions of stimulation and modulation.
Ca2+通道对兴奋-分泌偶联的调节是神经末梢的一项基本特性。能阻断特定类型Ca2+通道的肽类毒素已被用于确定哪些通道参与神经递质释放。对大鼠纹状体突触体释放的[3H]-谷氨酸和[3H]多巴胺进行亚秒级测量表明，对墨西哥漏斗蛛毒液肽ω-Aga-IVA敏感的P型通道可触发两种递质的释放。多巴胺（而非谷氨酸）的释放也受N型、对ω-芋螺毒素敏感的通道控制。在强去极化情况下，单独使用这两种毒素效果都不太显著，而ω-Aga-IVA和ω-芋螺毒素联合使用可对60 - 80%的Ca(2+)依赖性多巴胺释放产生协同抑制作用。结果表明，在大多数神经末梢的正常生理条件下，多种类型的Ca2+通道共同存在以调节神经分泌。多巴胺能末梢中P型和N型通道共存，而谷氨酸能末梢中P型通道与一种对ω-芋螺毒素和ω-Aga-IVA耐药的通道共存。这种排布可在不同的刺激和调节条件下为递质释放的调节提供高度的灵活性。
