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Volume 16, Number 23, Issue of December 1, 1996 pp. 7458-7468
Copyright ©1996 Society for Neuroscience

Two Alternatively Spliced Forms of the cGMP-Gated Channel -Subunit from Cone Photoreceptor Are Expressed in the Chick Pineal Organ

Received July 10, 1996; revised Sept. 5, 1996; accepted Sept. 12, 1996.

Wolfgang Bönigk¹, Frank Müller¹, Ralf Middendorff², Ingo Weyand¹, and U. Benjamin Kaupp¹

¹ Institut für Biologische Informationsverarbeitung, Forschungszentrum Jülich, D-52425 Jülich, Germany, and ² Anatomisches Institut, Universitätskrankenhaus Eppendorf, D-20246 Hamburg, Germany

Light sensitivity of the pineal has been retained in most vertebrates, except mammals. Retinal photoreceptors and pinealocytes share common components of light-dependent signaling pathways. In particular, an ion channel gated by cGMP has been electrophysiologically identified in chick pinealocytes; however, the physiological function of a light-sensitive enzyme cascade is not known, and primary structures of only a few pineal components have been determined. By PCR analysis and cloning of the respective cDNA, we show that the chick pineal expresses the -subunit of the cyclic nucleotide-gated (CNG) channel of rod photoreceptors and two short forms of the cone CNG channel. Analysis of the chick cone CNG channel gene reveals that these forms are produced by alternative splicing, which removes either one or two exons from the transcript. The shorter splice variant is functional when heterologously expressed, and it is approximately twofold more sensitive to activation by cGMP than the cone CNG channel. The chick cone CNG channel and the pineal splice form are both modulated by Ca²⁺/calmodulin (CaM). The CaM sensitivity might be mediated by a putative CaM-binding site in an N-terminal segment encoded by exon 4. This exon is missing in the gene for the rod CNG channel -subunit. Pineal CNG channels are candidates for receptor-mediated Ca²⁺ entry into pinealocytes and may be an important element of signaling pathways that control the light response and secretion of the pineal hormone melatonin.

Key words: ion channels; cyclic nucleotides; calmodulin; calcium; signal transduction; pineal gland

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