Neurite outgrowth from PC12 cells is enhanced by an inhibitor of mechanical channels.
GsMTx4, a peptide inhibitor for mechanosensitive ion channels (MSCs), promoted neurite outgrowth from PC12 cells in the presence of NGF in a dose-dependent manner between 5 and 100 microM peptide. Enhanced neurite growth required >12 h of peptide exposure in cells grown with NGF. Adsorption of GsMTx4 to serum proteins in the media lowered the free peptide concentration of 100 microM to a free concentration of 5 microM, a concentration shown to completely inhibit MSCs in the patch clamp assay. Outside-out patches from PC12 cells grown in NGF had mechanically activated cation channels that were reversibly inhibited by GsMTx4. These results are similar to those observed by Gomez and co-workers in Xenopus spinal cord. The inhibition of mechanosensitive channels by GsMTx4 may be a useful approach to accelerate regeneration of neurons in neurodegenerative diseases and spinal cord injury.
Gottlieb
Philip A
PA
Physiology and Biophysics, 301 Cary Hall, SUNY at Buffalo, Buffalo, NY 14214, USA. philgott@buffalo.edu
Barone
Tara
T
Sachs
Frederick
F
Plunkett
Robert
R
D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects*; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010455:Peptides / Q000494:pharmacology*; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology*; D013997:Time Factors
D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; C411249:MTx4 protein, Grammostola spatulata; D010455:Peptides; D013111:Spider Venoms; D020932:Nerve Growth Factor