Cote R H, Nicol G D, Burke S A, Bownds M D
J Biol Chem. 1986 Oct 5;261(28):12965-75.
Cyclic GMP has been implicated in controlling the light-regulated conductance of rod photoreceptors of the vertebrate retina. However, there is little direct evidence correlating changes in cGMP concentration with the light-regulated permeability mechanism in living cells. A preparation of intact frog rod outer segments suspended in a Ringer's medium containing low Ca2+ has been used to demonstrate that initial changes in total cellular cGMP concentration parallel changes in the light-regulated membrane current over a wide range of light intensities. At light intensities bleaching from 160 to 5.6 X 10(6) rhodopsin molecules/rod/s, decreases in the response latency for the cGMP kinetics parallel decreases in the latent period of the electrical response. Further, changes in the rate of the cGMP decrease parallel the rate of membrane current suppression as the light intensity is varied. Up to 10(5) cGMP molecules are hydrolyzed per photolyzed rhodopsin, consistent with in vitro studies showing that each bleached rhodopsin can activate over 100 phosphodiesterase molecules. Addition of the Ca2+ ionophore, A23187, does not affect the initial kinetics of the cGMP decrease or of the electrical response, excluding a direct role for Ca2+ in the initial events of phototransduction. These results are consistent with cGMP being the intracellular messenger that links rhodopsin isomerization with changes in membrane permeability upon illumination. It is unlikely, however, that light-induced changes in total cGMP concentration are the sole regulators of membrane current. This is suggested by several observations: at bright light intensities, the subsecond light-induced cGMP decrease is essentially complete prior to complete suppression of membrane current; maximal light-induced decreases in cGMP concentration occur at all light intensities tested, whereas the extent of membrane current suppression varies over the same range of light intensities; changing the external Ca2+ concentration from 1 mM to 10 nM in the dark causes an increase in membrane current that is significantly more rapid than corresponding changes in cGMP concentration. Thus, light-induced changes in total cellular cGMP concentration correlate with some, but not all, aspects of the visual excitation process in vertebrate photoreceptors.
环磷酸鸟苷（cGMP）被认为参与调控脊椎动物视网膜视杆光感受器的光调节电导。然而，几乎没有直接证据表明cGMP浓度的变化与活细胞中的光调节通透性机制相关。一种将完整的青蛙视杆外段悬浮于含低Ca2+的林格氏液中的制备方法已被用于证明，在广泛的光强度范围内，细胞内总cGMP浓度的初始变化与光调节膜电流的变化平行。在光强度从160漂白至5.6×10(6)个视紫红质分子/视杆/秒的过程中，cGMP动力学的反应潜伏期缩短与电反应潜伏期的缩短平行。此外，随着光强度变化，cGMP降低速率的变化与膜电流抑制速率平行。每个被光解的视紫红质可水解多达10(5)个cGMP分子，这与体外研究结果一致，即每个漂白的视紫红质可激活超过100个磷酸二酯酶分子。添加Ca2+离子载体A23187并不影响cGMP降低或电反应的初始动力学，排除了Ca2+在光转导初始事件中的直接作用。这些结果与cGMP作为细胞内信使的观点一致，该信使在光照时将视紫红质异构化与膜通透性变化联系起来。然而，光诱导的总cGMP浓度变化不太可能是膜电流的唯一调节因素。这由以下几个观察结果表明：在强光强度下，亚秒级的光诱导cGMP降低在膜电流完全抑制之前基本完成；在所有测试的光强度下，cGMP浓度的最大光诱导降低均会发生，而膜电流抑制程度在相同光强度范围内有所不同；在黑暗中将外部Ca2+浓度从1 mM变为10 nM会导致膜电流增加，其速度明显快于cGMP浓度的相应变化。因此，光诱导的细胞内总cGMP浓度变化与脊椎动物光感受器视觉兴奋过程的某些但并非所有方面相关。
