Selective Blocking of Voltage-Gated Sodium Channels in the Frog Optic Nerve
Restricted (Penn State Only)
- Author:
- Hallahan, Dana
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Elizabeth Anne Dudkin, Thesis Supervisor
Hans Schmidt, Thesis Honors Advisor - Keywords:
- Voltage-Gated Sodium Channels
Frog
Visual System
Optic Nerve
Optic Tectum
Retina
Nav
Prilocaine
Gene
Gene Sequences
TTX
Tetrodotoxin
Selective Blocking
Toxins - Abstract:
- Frogs exhibit visually guided behaviors, including prey-catching and threat avoidance, that are controlled by the optic tectum via the optic nerve (Ingle, 1973). King et al. (1999) selectively blocked voltage-gated sodium channels (Navs) using cadmium chloride and tetrodotoxin and found that threat avoidance behavior was eliminated while prey-catching behavior was preserved. This indicates that these two behaviors are processed by different fibers. This project aims to identify drugs that selectively eliminate frogs' prey-catching behavior. BLAST was used to compare Nav gene sequences from Xenopus tropicalis and Homo sapiens to determine the best Nav blockers. The xt28 gene in X. tropicalis was compared to the SCN5A, SCN10A, and SCN11A genes in H. sapiens, and results showed that the TTX-resistant Nav 1.5 gene (SCN5A) in H. sapiens had the highest similarity to the xt28 gene at 68.68%, followed by Nav 1.8 (SCN10A; 59.78%), and Nav 1.9 (SCN11A; 55.08%) channels. The Nav 1.5 gene sequence of Rana temporaria was also compared to both H. sapiens and X. tropicalis, finding similarities between the Nav gene in both frog species (86.69%) and showing consistency with human Nav evolution (67.66%) (National Center for Biotechnology Information, n.d.; Zakon et al., 2011). The best candidate for the experiment is Prilocaine due to its specificity in blocking Nav 1.5, its reversible ability, and its injectable nature (DrugBank Online, n.d.-a).