Effects of 4-aminopyridine on protein phosphorylation in heat-blocked peripheral nerve.
The topical application of 4-aminopyridine (4-AP) reverses within 1-3 min the partial conduction block that results from heating 5-mm segments of rat posterior tibial, peroneal and sural nerves to 45 degrees C for several minutes. Nerves previously blocked in vitro or in vivo were incubated in vitro in the presence of [gamma-32P]ATP. The rate of phosphorylation of soluble nerve proteins that had entered the media was determined. Labeled proteins were separated electrophoretically and autoradiograms prepared. We found that 5 mM 4-AP increases the phosphorylation rate in heat-blocked nerve by approximately 50-fold. The process is calcium-dependent and is heat-labile. Soluble proteins with a molecular weight in the 53-55 kDa range are preferentially but not exclusively phosphorylated in the presence of 4-AP at levels effective in restoring conduction. The results suggest that the potassium channel blocker 4-AP may restore conduction by inducing changes in channel proteins.
Eliasson
S G
SG
Department of Neurology and Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110.
Monafo
W W
WW
D015761:4-Aminopyridine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D006358:Hot Temperature; D007700:Kinetics; D008970:Molecular Weight; D009407:Nerve Block; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism*; D010543:Peroneal Nerve / Q000378:metabolism; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D013497:Sural Nerve / Q000378:metabolism; D013979:Tibial Nerve / Q000378:metabolism
D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D002118:Calcium