The permeability of the cGMP-activated channel to organic cations in retinal rods of the tiger salamander

1. The permeability of the channel activated by guanosine 3',5'‐cyclic monophosphate (cGMP) to many organic monovalent cations was determined by recording macroscopic currents in excised inside‐out patches of plasma membrane from isolated retinal rod outer segments of the tiger salamander. 2. Current‐voltage relations were measured when the NaCl of the bathing medium was replaced by salts of organic cations. Permeability ratios relative to Na+ ions were calculated with the Goldman‐Hodgkin‐Katz potential equation from the measured changes of reversal potentials. 3. Hydroxylammonium+, hydrazinium+ and methylammonium+, which are molecules of very similar shape and size, permeate the channel with very different permeability ratios: 5.92, 1.99 and 0.60 respectively. 4. Methylated and ethylated ammonium+ compounds were investigated. It was found that, not only methylammonium+, but also dimethylammonium+ and ethylammonium+ were permeant with permeability ratios of 0.6, 0.14 and 0.16 respectively. Trimethylammonium+, tetramethylammonium+, diethylammonium+, triethylammonium+, and tetraethylammonium+ were not permeant. 5. Guanidinium+ and its derivatives formamidinium+, aminoguanidinium+, acetamidinium+ and methylguanidinium+ were all permeant with permeability ratios 1.12, 1.00, 0.63, 0.36 and 0.33 respectively. 6. The cGMP‐activated channel was found to be permeable to at least thirteen organic cations. Molecular models of the permeant cations indicate that the cross‐section of the narrowest part of the pore must be at least as large as a rectangle of 0.38 x 0.5 nm dimensions.