Ca2F permeation in cyclic nucleotide-gated channels

Cyclic nucleotide-gated (CNG) channels conduct NaF, KF and Ca2F 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 Ca2F 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 Ca2F signaling depends on its specific Ca2F conductance, it is necessary to analyze Ca2F permeation for each individual channel type. We have analyzed Ca2F permeation in all principal subunits of vertebrates and for a principal subunit from Drosophila melanogaster. We measured the fractional Ca2F current over the physiological range of Ca2F concentrations and found that Ca2F permeation is determined by subunit composition and modulated by membrane voltage and extracellular pH. Ca2F permeation is controlled by the Ca2F-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 Ca2F signals.