title: Effect of amyotrophic lateral sclerosis serum on calcium channels related to spontaneous acetylcholine release.
abstract: OBJECTIVE
  The aim of this work was to further investigate the effect of sera from sporadic amyotrophic lateral sclerosis (ALS) patients on miniature end-plate potentials (MEPP) frequency, by the mouse passive transfer model, and to study whether the transferred serum induces any change in the sensitivity of the L-type voltage-dependent calcium channels (VDCC) to its specific blocker Nitrendipine.
  
  
  METHODS
  A total of 35 CF1 mice were divided into 3 groups: (a) ALS group receiving sera from 15 patients that had been clinically and electromyographycally diagnosed as having sporadic ALS; (b) normal group receiving sera from 13 healthy volunteers and from 3 disease control patients, and (c) control group, which was kept untreated. Animals in groups (a) and (b) received daily intraperitoneal injection of 0.5-1ml of serum for 3 days, and 24h later the left hemidiaphragm was excised for electrophysiological recordings.
  
  
  RESULTS
  Analysis of MEPPs frequency recorded from ALS group showed that 3 of them induced an increase in spontaneous neurotransmitter release while in 4 a decrease was observed, suggesting that sera alter spontaneous secretion as result of an increased or decreased Ca(2+) influx through the normally involved N-type or L-type VDCC, respectively. When the effect of Nitrendipine, an L-type VDCC blocker, was studied on ALS sera-injected mice, we found variable responses to the drug: only two mice showed control sensitivity to Nitrendipine, while in 7 its action was lower and surprisingly in 4 was greater than that without the drug.
  
  
  CONCLUSIONS
  These results suggest that ALS sera contain factor(s) that are able to modify spontaneous neurotransmitter release by altering calcium current through L-type and N-type VDCC, and even inducing changes in the sensitivity to the L-type VDCC blocker.
authors.affiliation: Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, Argentina. smuchnik@roche.com.ar
authors.forename: Salomón
authors.initials: S
authors.lastname: Muchnik
authors.forename: Adriana
authors.initials: A
authors.lastname: Losavio
authors.forename: Silvana
authors.initials: S
authors.lastname: De Lorenzo
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D003964:Diaphragm / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008875:Middle Aged; D009045:Motor Endplate / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009568:Nitrendipine / Q000494:pharmacology; D013696:Temperature
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009568:Nitrendipine; D000109:Acetylcholine