Womble M D, Wickelgren W O
Department of Physiology, University of Colorado Health Sciences Center, Denver 80262.
Brain Res. 1990 Jun 4;518(1-2):135-42. doi: 10.1016/0006-8993(90)90964-d.
Intracellular recordings from primary mechanosensory neurons (dorsal cells) of the lamprey spinal cord were made to test the membrane effects of forskolin, an activator of adenylate cyclase in these cells. At a concentration of 50 microM, forskolin was found to have a pronounced broadening effect on calcium action potentials (Ca APs) produced in the presence of voltage-activated K channel blockers (TEA, 3,4-DAP). Forskolin had no effect on passive membrane properties of the cells, such as resting potential or input resistance. Nor did it affect delayed rectification or Na APs and thus appeared not to block voltage-activated K channels. Forskolin's effect was evident only when a significant Ca component to the AP was present. It appeared not to increase the conductance of the Ca channel since its action was accompanied by a decrease in membrane conductance during the Ca AP, indicating instead an inhibition of a repolarizing Ca-activated conductance, other than a Ca-activated Cl conductance. The prolongation of Ca APs by forskolin, barium or the neurotransmitter GABA were all correlated in voltage-clamp with a decrease in outward current. Under the conductions used here, the major outward conductance in dorsal cells is a Ca-activated K conductance (gK(Ca]28, and it is concluded that the most probable mode of action for forskolin is via a cyclic AMP-mediated inhibition of this conductance. GABA has also been shown to prolong Ca APs in lamprey dorsal cells by inhibiting a repolarizing gK(Ca)28. Thus, the action of this transmitter may be mediated by an increase in intracellular cyclic AMP.
对七鳃鳗脊髓的初级机械感觉神经元（背侧细胞）进行细胞内记录，以测试福斯高林（这些细胞中腺苷酸环化酶的激活剂）对膜的影响。在浓度为50微摩尔时，发现福斯高林对在电压激活钾通道阻滞剂（四乙铵、3,4-二氨基吡啶）存在下产生的钙动作电位（Ca APs）有明显的展宽作用。福斯高林对细胞的被动膜特性，如静息电位或输入电阻没有影响。它也不影响延迟整流或钠动作电位，因此似乎不会阻断电压激活钾通道。福斯高林的作用仅在动作电位存在显著钙成分时才明显。它似乎没有增加钙通道的电导，因为其作用伴随着钙动作电位期间膜电导的降低，这表明它抑制的是一种复极化钙激活电导，而不是钙激活氯电导。福斯高林、钡或神经递质γ-氨基丁酸（GABA）对钙动作电位的延长在电压钳中均与外向电流的降低相关。在本文所用的条件下，背侧细胞中的主要外向电导是钙激活钾电导（gK(Ca)），由此得出结论，福斯高林最可能的作用方式是通过环磷酸腺苷（cAMP）介导抑制这种电导。γ-氨基丁酸也已被证明通过抑制复极化的gK(Ca)来延长七鳃鳗背侧细胞的钙动作电位。因此，这种神经递质的作用可能是由细胞内环磷酸腺苷的增加介导的。
