Cationic peptides (polylysines and polyarginines) are being developed as drug delivery systems to nuclei.
Therefore, a detailed description of tissue response changes upon the application of cationic peptides over intact basement
membranes of excitable tissue is of interest in pharmacology. In this paper we examine the effects of two naturally occurring
cationic peptides protamine (polyarginine) and crotamine (polylysine) on the optical profiles of retinal spreading depression
waves (RSDs). This intrinsic optical signal (IOS), recorded non-invasively, provides information about dissipation
of electrochemical gradients within the tissue and its metabolic consequences. Protamine at nanomolar range brought
the tissue excitability to collapse without any signs of acute toxicity whereas crotamine, a known myotoxin from rattlesnake,
decreased the tissue transparency and changed markedly the optical profiles of RSDs. Also, fluorescent crotamine
was incorporated to Müller cells in a few minutes, suggesting a close membrane interaction. The optical changes brought
about by crotamine were easily washed off. By contrast, the excitability collapse in presence of protamine lasted for at
least two hours. Conclusions: we concluded that crotamine has fusogenic properties that alters ion transport in excitable
tissue. Protamine effect seems to be similar to its effect on basement membrane of epithelium due to its property of making
heteropolymers with heparan sulfate. The clinical syndrome expressed in mice after crotamine injection suggested excitotoxic
CNS effects confirmed by the isolated retina experiments.
Keywords: Crotamine, drug delivery systems, excitable media, global coupling, intrinsic optical signals, Na-KATPase, protamine,
retinal spreading depression.
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