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The Journal of Neuroscience, February 15, 2000, 20(4):1324-1332

Molecular Cloning and Functional Characterization of a New Modulatory Cyclic Nucleotide-Gated Channel Subunit from Mouse Retina

Andrea Gerstner¹, Xiangang Zong¹, Franz Hofmann¹, and Martin Biel^{1, 2}

¹ Institut für Pharmakologie und Toxikologie der Technischen Universität München, 80802 München, Germany, and ² Institut für Pharmazie-Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München, 81377 München, Germany

Cyclic nucleotide-gated (CNG) channels play a key role in olfactory and visual transduction. Native CNG channels are heteromeric complexes consisting of the principal  subunits (CNG1-3), which can form functional channels by themselves, and the modulatory  subunits (CNG4-5). The individual  and  subunits that combine to form the CNG channels in rod photoreceptors (CNG1 + CNG4) and olfactory neurons (CNG2 + CNG4 + CNG5) have been characterized. In contrast, only an  subunit (CNG3) has been identified so far in cone photoreceptors. Here we report the molecular cloning of a new CNG channel subunit (CNG6) from mouse retina. The cDNA of CNG6 encodes a peptide of 694 amino acids with a predicted molecular weight of 80 kDa. Among the CNG channel subunits, CNG6 has the highest overall similarity to the CNG4  subunit (47% sequence identity). CNG6 transcripts are present in a small subset of retinal photoreceptor cells and also in testis. Heterologous expression of CNG6 in human embryonic kidney 293 cells did not lead to detectable currents. However, when coexpressed with the cone photoreceptor  subunit, CNG6 induced a flickering channel gating, weakened the outward rectification in the presence of extracellular Ca²⁺, increased the sensitivity for L-cis diltiazem, and enhanced the cAMP efficacy of the channel. Taken together, the data indicate that CNG6 represents a new CNG channel  subunit that may associate with the CNG3  subunit to form the native cone channel.

Key words: cone photoreceptor; cyclic nucleotide; cation channel; L-cis diltiazem; single-channel recording

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Copyright © 2000 Society for Neuroscience  0270-6474/00/2041324-09$05.00/0

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