Ionic selectivity of I_h channels of rod photoreceptors in tiger salamanders

Ionic selectivity of I_h channels of tiger salamander rod photoreceptors was investigated using whole-cell voltage clamp. Measured reversal potentials and the Goldman-Hodgkin-Katz voltage equation were used to calculate permeability ratios with 20 mM K⁺ as a reference. In the absence of external K⁺, I_h is small and hard to discern. Hence, we defined I_h as the current blocked by 2 mM external Cs⁺. Some small amines permeate I_h channels, with the following permeability ratios (P_X/.P_K):NH₄⁺, 0.17; methylammonium, 0.06; and hydrazine, 0.04. Other amines are tially impermeant: dimethylammonium (<0.02), ethylammonium (<0.01), and tetramethylammonium (<0.01). When K⁺ is the only external permeant ion and its concentration is varied, the reversal potential of I_h follows the Nernst potential for a K⁺ electrode, I_h channels are also permeable to other alkali metal cations (P_x/P_K): Tl⁺, > 1.55; K⁺, 1; Rb⁺, >0.55; Na⁺, 0.33; Li⁺, 0.02. Except for Na⁺, the relative slope conductance had a similar sequence (G_X/G_K): Tl⁺, 1.07; K⁺, 1; Rb⁺, 0.37; NH₄⁺, 0.07; Na⁺, 0.02. Based on permeabilities to organic cations, the narrowest part of the pore has a diameter between 4.0 and 4.6 Å. Some permeant cations have large effects on the gating kinetics of I_h channels; however, permeant cations appear to have little effect on the steady-state activation curve of I_h, channels. Lowering K⁺ or replacing K⁺ with Na⁺ reduces the maximal conductance of I_h but does not shift or change the steepness of its voltage dependence. With ammonium or methylammonium replacing K⁺ a similar pattern is seen, except that there is a small positive shift of ∼ 10 mV in the voltage dependence.