The regulation of the retrograde axonal transport of I-β nerve growth factor is independent of calcium

Calcium has been shown to play a major role in the regulation of endocytosis and exocytosis of synaptic vesicles and retrograde axonal transport of proteins. The role of calcium in the regulation of neurotrophin retrograde axonal transport is unknown. This study aimed to determine if calcium plays a role in the uptake and retrograde axonal transport of ¹²⁵I-β nerve growth factor (¹²⁵I-βNGF) within sympathetic neurons innervating the iris by comparing it with ¹²⁵I-anti-dopamine beta hydroxylase (anti-DBH). The nonspecific voltage-sensitive calcium channel (VSCC) antagonists, cadmium (200 nmol/eye) and nickel (100 nmol/eye) reduced the amount of ¹²⁵I-anti-DBH retrograde axonal transport by 90 and 70%, respectively. In contrast, cadmium (200 nmol/eye) had no effect on ¹²⁵I-βNGF retrograde axonal transport, while nickel (100 nmol/eye) caused a significant increase in the amount transported to the ganglia. The L-type VSCC antagonist nifedipine (10 nmol/eye) and N-type VSCC antagonist omega-conotoxin (1.5 nmol/eye) both had no effect on ¹²⁵I-anti-DBH retrograde axonal transport which suggests that these types of calcium channels are not involved in the exocytosis/endocytosis of anti-DBH containing vesicles. Thapsigargin (0.2 nmol/eye), an inhibitor of sarcoplasmic reticulum Ca²⁺-ATPases also significantly inhibited ¹²⁵I-anti-DBH transport but had no effect on ¹²⁵I-βNGF retrograde transport. This suggests that ¹²⁵I-anti-DBH and ¹²⁵I-βNGF are internalized into different vesicle types and that the endocytosis and retrograde axonal transport of ¹²⁵I-βNGF are not dependent upon calcium.