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Gating of Cyclic Nucleotide-Gated (CNGA1) Channels by cGMP Jumps and Depolarizing Voltage Steps

Vasilica Nache ^*, Jana Kusch ^*, Volker Hagen  and Klaus Benndorf ^*

^* Institut für Physiologie II, Friedrich-Schiller-Universität Jena, Jena, Germany; and Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany

Correspondence: Address reprint requests to Dr. K. Benndorf, Friedrich-Schiller-Universität Jena, Institut für Physiologie II, Kollegiengasse, 9 D-07743 Jena, Germany. Tel.: 49-3641-934351; Fax: 49-3641-933202; E-mail: Klaus.Benndorf{at}mti.uni-jena.de.

We expressed rod-type homotetrameric cyclic nucleotide-gated (CNGA1) channels in Xenopus oocytes and studied activation by photolysis-induced jumps of the 3',5'-cyclic guanosine monophosphate (cGMP) concentration and by voltage steps. cGMP jumps to increasing concentrations up to the EC₅₀ value of 46.5 µM decelerate the activation gating, indicative that even at concentrations of cGMP <<EC₅₀ binding is not rate limiting. Above the EC₅₀ value, activation by cGMP jumps is again accelerated to the higher concentrations. At the same cGMP concentration, the speed of the activation gating by depolarizing voltage steps is roughly similar to that by cGMP jumps. Permeating ions passing the pore more slowly (Rb⁺ > K⁺ > Na⁺) slow down the activation time course. At the single-channel level, cGMP jumps to high concentrations cause openings directly to the main open level without passing sublevels. From these results it is concluded that at both low and high cGMP the gating of homotetrameric CNGA1 channels is not rate-limited by the cGMP binding but by conformational changes of the channel which are voltage dependent and include movements in the pore region.