Castro N G, Albuquerque E X
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201-1559.
Biophys J. 1995 Feb;68(2):516-24. doi: 10.1016/S0006-3495(95)80213-4.
The hippocampal nicotinic acetylcholine receptor (nAChR) is a newly identified ligand-gated ion channel that is blocked by the snake toxin alpha-bungarotoxin (alpha-BGT) and that probably contains the alpha 7 nAChR subunit in its structure. Here its ion selectivity was characterized and compared with that of the N-methyl-D-aspartate (NMDA) receptor channel. The reversal potentials (VR) of acetylcholine- and NMDA-activated whole-cell currents were determined under various ionic conditions. Using ion activities and a Goldman-Hodgkin-Katz equation for VR shifts in the presence of Ca2+, permeability ratios were calculated. For the alpha-BGT-sensitive nAChR, PNa/PCs was close to 1 and Cl- did not contribute to the currents. Changing the [Ca2+]0 from 1 to 10 mM, the VRs of the nAChR and NMDA currents were shifted by +5.6 +/- 0.4 and +8.3 +/- 0.4 mV, respectively, and the nAChR current decay was accelerated. These shifts yielded PCa/PCss of 6.1 +/- 0.5 for the nAChR channel and 10.3 +/- 0.7 for the NMDA channel. Thus, the neuronal alpha-BGT-sensitive nAChR is a cation channel considerably selective to Ca2+ and may mediate a fast rise in intracellular Ca2+ that would increase in magnitude with membrane hyperpolarization.
海马体烟碱型乙酰胆碱受体(nAChR)是一种新发现的配体门控离子通道,可被蛇毒素α-银环蛇毒素(α-BGT)阻断,其结构中可能含有α7 nAChR亚基。在此对其离子选择性进行了表征,并与N-甲基-D-天冬氨酸(NMDA)受体通道的离子选择性进行了比较。在各种离子条件下测定了乙酰胆碱和NMDA激活的全细胞电流的反转电位(VR)。利用离子活度和存在Ca2+时VR位移的戈德曼-霍奇金- Katz方程,计算了通透率比。对于α-BGT敏感的nAChR,PNa/PCs接近1,Cl-对电流无贡献。将[Ca2+]0从1 mM变为10 mM时,nAChR和NMDA电流的VR分别偏移+5.6±0.4和+8.3±0.4 mV,且nAChR电流衰减加速。这些偏移得出nAChR通道的PCa/PCss为6.1±0.5,NMDA通道的为10.3±0.7。因此,神经元α-BGT敏感的nAChR是一种对Ca2+具有相当选择性的阳离子通道,可能介导细胞内Ca2+的快速升高,这种升高会随着膜超极化而幅度增加。