Cellular mechanisms underlying the pharmacological induction of phosphenes

• Published in: British journal of pharmacology Vol. 150; no. 4; pp. 383 - 390
• Main Authors: Cervetto, L, Demontis, G C, Gargini, C
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-02-2007; Nature Publishing; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; HCN channels; heart rate‐lowering drugs; Humans; hyperpolarization activated currents (If, Ih); If and Ih inhibitors; ivabradine; Medical sciences; Ophthalmology; Pharmacology. Drug treatments; phosphene induction; phosphene perception; Phosphenes - drug effects; Photic Stimulation; Photoreceptor Cells, Vertebrate - physiology; Review; Vision disorders; Visual Cortex - physiology; Drug; Phosphene; Induction; Vision disorder; Ivabradine; Antiarrhythmic agent; In vitro; Heart rate; phosphene perception; phosphene induction; ivabradine; HCN channels; hyperpolarization activated currents If; Eye disease; Perception; Inhibitor; Ih; If and Ih inhibitors; heart rate-lowering drugs; Mechanism of action; Hyperpolarization
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0706998

Visual sensations evoked by stimuli other than luminance changes are called phosphenes. Phosphenes may be an early symptom in a variety of diseases of the retina or of the visual pathways, but healthy individuals may perceive them as well. Phosphene‐like phenomena are perhaps the most common side effect reported in clinical pharmacology. Ivabradine, a novel anti‐anginal drug that reduces heart‐rate by inhibiting the hyperpolarization activated current expressed in cardiac sinoatrial node cells (If) induces phosphenes in some patients. One hypothesis is that ivabradine interacts with the visual system by inhibiting hyperpolarization‐activated current in retinal cells (Ih). An Ih current with properties similar to cardiac If has been reported in retinal neurones. Under normal circumstances most of the random fluctuations generated within the retinal circuits do not reach the level of conscious perception because they are filtered out. Presumably, filtering occurs mostly within the retina and one serious candidate for this action is the ability of Ih to act as a negative‐feedback mechanism. Ih activation in the membrane of visual cells causes dampening of responses to slow noisy inputs thus tuning the visual system to perceptually more relevant signals of higher frequency. Ih inhibition, by altering at the retinal synapses the filtering of signals generated by thermal breakdown of rhodopsin or other fluctuations, is expected to increase the probability of phosphene occurrence. It is the purpose of the present paper to outline and discuss the features of the visual system and the pharmacological conditions relevant to phosphene perception.
British Journal of Pharmacology (2007) 150, 383–390. doi:10.1038/sj.bjp.0706998