Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins

Author(s): Welch MJ1, Purkiss JR, Foster KA

Abstract

Clostridium botulinum neurotoxins (BoNT) are zinc dependent endopeptidases which, once internalised into the neuronal cytosol, block neurotransmission by proteolysis of membrane-associated proteins putatively involved in synaptic vesicle docking and fusion with the plasma membrane. Although many studies have used a variety of cellular systems to study the neurotoxins, most require relatively large amounts of toxin or permeabilisation to internalise the neurotoxin. We present here a primary culture of embryonic rat dorsal root ganglia (DRG) neurons that exhibits calcium-dependent substance P secretion when depolarised with elevated extracellular potassium and is naturally BoNT sensitive. The DRG neurons showed a different IC50 for each of the toxins tested with a 1000 fold difference between the most and least potent neurotoxins (0.05, 0.3, 30 and approximately 60 nM for A, C, F and B, respectively). BoNT/A cleavage of SNAP-25 was seen as early as 2 h, but substance P secretion was not significantly inhibited until 4 h intoxication and the effects of BoNT/A were observed for as long as 15 days. This primary neuronal culture system represents a new and sensitive cellular model for the in vitro study of the botulinum neurotoxins.

Similar Articles

Ankle osteoarthritis scale

Author(s): Domsic RT1, Saltzman CL

Clinical rating systems for the ankle-hindfoot, midfoot, hallux, and lesser toes

Author(s): Kitaoka HB1, Alexander IJ, Adelaar RS, Nunley JA, Myerson MS, et al.

Unipedal stance testing as an indicator of fall risk among older outpatients

Author(s): Hurvitz EA1, Richardson JK, Werner RA, Ruhl AM, Dixon MR

Efficacy of intra-articular botulinum toxin type A in painful knee osteoarthritis: a pilot study

Author(s): Boon AJ1, Smith J, Dahm DL, Sorenson EJ, Larson DR, et al.

Neurogenic aspects of inflammation

Author(s): Schaible HG1, Del Rosso A, Matucci-Cerinic M

Pathophysiology and treatment of pain in joint disease

Author(s): Schaible HG1, Schmelz M, Tegeder I

Reduced muscle function in patients with osteoarthritis

Author(s): Fisher NM1, Pendergast DR