OKADAIC ACID INDUCES THE RAPID AND REVERSIBLE DISRUPTION OF THE NEUROFILAMENT NETWORK IN RAT DORSAL-ROOT GANGLION NEURONS

Treatment of 15-17 day old dissociated cultures of rat dorsal root ganglia with 1 μM okadaic acid caused a reduction in the mobilities of neurofilament subunits on SDS-polyacrylamide gels, signifying an increase in their phosphorylation levels. When cultures were exposed to okadaic acid for 0.5 hrs and harvested in buffer containing Triton X-100, NF-H was nearly completely redistributed to the detergent- soluble fraction while NF-M and NF-L required a longer exposure to the drug before undergoing a similar shift. This redistribution of subunits corresponded with striking changes in the immunofluorescence staining pattern for neurofilaments. Upon removal of okadaic acid from the culture medium following a 0.5 hr treatment, NF-L and NF-M returned to the Triton X-100 insoluble fraction within 2 hrs while NF-H required 10 hrs for recovery. © 1992 Academic Press, Inc.