Dzeja C, Hagen V, Kaupp U B, Frings S
Institut für Biologische Informationsverarbeitung, Forschungszentrum Jülich, 52425 Jülich.
EMBO J. 1999 Jan 4;18(1):131-44. doi: 10.1093/emboj/18.1.131.
Cyclic nucleotide-gated (CNG) channels conduct Na+, K+ and Ca2+ currents under the control of cGMP and cAMP. Activation of CNG channels leads to depolarization of the membrane voltage and to a concomitant increase of the cytosolic Ca2+ concentration. Several polypeptides were identified that constitute principal and modulatory subunits of CNG channels in both neurons and non-excitable cells, co-assembling to form a variety of heteromeric proteins with distinct biophysical properties. Since the contribution of each channel type to Ca2+ signaling depends on its specific Ca2+ conductance, it is necessary to analyze Ca2+ permeation for each individual channel type. We have analyzed Ca2+ permeation in all principal subunits of vertebrates and for a principal subunit from Drosophila melanogaster. We measured the fractional Ca2+ current over the physiological range of Ca2+ concentrations and found that Ca2+ permeation is determined by subunit composition and modulated by membrane voltage and extracellular pH. Ca2+ permeation is controlled by the Ca2+-binding affinity of the intrapore cation-binding site, which varies profoundly between members of the CNG channel family, and gives rise to a surprising diversity in the ability to generate Ca2+ signals.
环核苷酸门控（CNG）通道在cGMP和cAMP的控制下传导Na+、K+和Ca2+电流。CNG通道的激活导致膜电压去极化，并伴随胞质Ca2+浓度的增加。已鉴定出几种多肽，它们构成神经元和非兴奋性细胞中CNG通道的主要和调节亚基，共同组装形成具有不同生物物理特性的多种异源蛋白。由于每种通道类型对Ca2+信号传导的贡献取决于其特定的Ca2+电导率，因此有必要分析每种单独通道类型的Ca2+通透情况。我们分析了脊椎动物所有主要亚基以及果蝇的一个主要亚基的Ca2+通透情况。我们在Ca2+浓度的生理范围内测量了Ca2+电流分数，发现Ca2+通透由亚基组成决定，并受膜电压和细胞外pH调节。Ca2+通透由孔内阳离子结合位点的Ca2+结合亲和力控制，该亲和力在CNG通道家族成员之间有很大差异，并导致产生Ca2+信号的能力出现惊人的多样性。
