Fast axonal transport is modulated by altering trans-axolemmal calcium flux.
Factors involved in fast axonal transport (motor proteins, microtubules, organelles, etc.) have been identified but the molecular mechanism controlling transport is unknown. We used video enhanced microscopy to directly evaluate the effect of calcium on fast axonal transport (FAxT). FAxT alterations included rapid speed decreases (within minutes) in Ca2+ free buffer and rapid speed increases (within seconds) when axons were treated with parathyroid hormone, BAY K 8644, or K+ depolarization. The speed increases were blocked by dihydropyridine Ca2+ channel antagonists. Ryanodine (20 microM), known to block calcium release from subcellular stores, caused a decrease in the rate of retrograde FAxT. Calcium ionophore A23187 (at 1 and 20 micrograms/ml) caused increases in FAxT, an effect also noted only in retrograde moving organelle traffic. Hyper- or hypo-tonic solutions produced no alterations making axoplasmic viscosity changes an unlikely explanation for the speed changes. Reproducible alteration of FAxT by manipulation of Ca2+ levels provides evidence that Ca2+ modulates fast axonal transport. Retrograde transport appears more sensitive to changes in Ca2+ and differential effects on antero- and retro-FAxT mechanisms suggest directional specificity for some of these signals which may be based upon the organelle size. Endogenous substances (e.g. PTH) that trigger axonal Ca2+ changes may rapidly modulate the rate of material delivery in axons. The results are discussed within the context of a Ca2+/calmodulin-dependent modification of the cytoskeletal matrix.
Breuer
A C
AC
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio.
Bond
M
M
Atkinson
M B
MB
D000818:Animals; D001369:Axons / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D004095:Dihydropyridines; D010281:Parathyroid Hormone; D002118:Calcium