Mechanism of Ba²⁺ block of M-like K channels of rod photoreceptors of tiger salamanders

I_Kx is a voltage-dependent K⁺ current in the inner segment of rod photoreceptors that shows many similarities to M-current. The depression of I_KX by external Ba₂₊ was studied with whole-cell voltage clamp. Ba²⁺ reduced the conductance and voltage sensitivity of I_KX tail currents and shifted the voltage range over which they appeared to more positive potentials. These effects showed different sensitivities to Ba²⁺: conductance was the least sensitive (K_0.5 = 7.6 mM), voltage dependence intermediate (K_0.5 = 2.4 mM) and voltage sensitivity the most sensitive (K_0.5 = 0.2 mM). Ca²⁺, Co²⁺, Mn²⁺, Sr²⁺, and Zn²⁺ did not have actions comparable to Ba²⁺ on the voltage dependence or the voltage sensitivity of I_KX tail currents. In high K⁺ (100 mM), the voltage range of activation of I_Kx was shifted 20 mV negative, as was the τ-voltage relation. High K⁺ did not prevent the effect of Ba²⁺ on conductance, but abolished its ability to affect voltage dependence and voltage sensitivity. Ba²⁺ also altered the apparent time-course of activation and deactivation of I_KX. Low Ba²⁺ (0.2 mM) slowed both deactivation and activation, with most effect on deactivation; at higher concentrations (1-25 mM), deactivation and activation time courses were equally affected, and at the highest concentrations, 5 and 25 mM Ba²⁺, the time course became faster than control. Rapid application of 5 mM Ba²⁺ suggested that the time dependent currents in Ba²⁺ reflect in part the slow voltage-dependent block and unblock of I_Kx channels by Ba²⁺. This blocking action of Ba²⁺ was steeply voltage-dependent with an apparent electrical distance of 1.07. Ba²⁺ appears to interact with I_KX channels at multiple sites. A model which assumes that Ba²⁺ has a voltage-independent and a voltage-dependent blocking action on open or closed I_KX channels reproduced many aspects of the data; the voltage-dependent component could account for both the Ba²⁺-induced shift in voltage dependence and reduction in voltage sensitivity of I_KX tail currents.