Modulation by hyperpolarization-activated cationic currents of voltage responses in human rods

We used the whole-cell patch-clamp recording technique on surgically excised human retina to examine whether human rod photoreceptors express hyperpolarization-activated cationic currents (I_h) and to analyze the effects of I_h on rod's voltage responses. Hyperpolarizing voltage steps from a holding potential of -60 mV evoked a slow inward-rectifying current in both rods in retinal slices and isolated rods. The slow inward-rectifying currents induced by hyperpolarization were markedly reduced by 3 mM Cs⁺ (a blocker of I_h) in the bath, but not by 3 mM Ba²⁺ (an anomalous rectifier K⁺ current blocker) or 1 mM SITS (a Cl^- current blocker). A concentration-response curve for block by Cs⁺ of the inward currents could be fitted by the Hill equation with a half-blocking concentration (IC₅₀) of 41 μM and a Hill coefficient of 0.91. The time course of the inward current activation was well described at all recorded voltages by the sum of two exponentials. Under current-clamp conditions, injection of steps of current, either hyperpolarizing or depolarizing, elicited an initial rapid voltage change that was followed by a gradual decay in the voltage response. The decay in the voltage responses was eliminated by bath application of 3 mM Cs⁺. The voltage dependence, pharmacology, and kinetics of the slow inward-rectifying currents described above suggest that human rods express I_h. We suggest that I_h becomes activated in the course of large hyperpolarizations generated by bright-light illumination and may modify the waveform of the photovoltage in human rods.