The different actions of two I(h) channel blockers, zatebradine (UL-FS 49) and ZD7288, on rod photoresponses were analysed by computer simulation using a newly revised ionic current model of the rod photoreceptor, based on Hodgkin-Huxley equations. The model, adjusted to fit the experimental results of amphibian rods, shows that both of the blockers enhance the light-induced membrane hyperpolarization. Our model can also predict a mechanism of a damped oscillation arising during the recovery phase appeared only in the presence of zatebradine which, unlike ZD7288, reduces both I(h) and I(Kv). We suggest that the oscillation can appear due to the alternative activation of voltage-dependent Ca(2+) current (I(Ca)) and calcium-dependent current (I(K(Ca)) and I(Cl(Ca))) when I(Kv) is blocked, with I(K(Ca)) having a stronger effect than I(Cl(Ca)).
