THE IMPACT OF ORGANIC INHIBITORS OF THE HYPERPOLARIZATION ACTIVATED CURRENT (I_H) ON THE ELECTRORETINOGRAM (ERG) OF RODENTS

摘要

Zatebradine, a bradycardic organic compound known to suppress the hyperpolar-ization activated current (Ih or If) in both cardiomyocytes (5) and retinal rods (2), when administered in cats by intravenous injection in amounts of 0.5-2 mg/Kg, reduces the ERG amplitude in response to periodic changes in luminance. This effect is especially prominent with stimuli of high mean luminance, sinusoidally modulated at high contrast (6, 7). The suppression of the high frequency component of the response characteristics of the electroretinogram (ERG) has been interpreted as a direct consequence of the suppression of the I_h current in both photoreceptors and second order retinal neurons, where I_h plays an important role in the band-pass amplification of visual signals (3). On the basis of psychophysical measurements carried out on healthy human subjects, it has been suggested that blockade of I_h in retinal neurons may account for the subjective visual effects reported by patients treated with bradicardic compounds (8). In view of the potential impact of these observations on the development of bradycardic drugs with reduced visual side effects, it is of interest to compare both visual and cardiac activity of other molecules known to possess I_h inhibiting properties.