Abnormal transmitter release at neuromuscular junctions of mice carrying the tottering alpha1A Ca2+ channel mutation

J. J. Plomp
2000 Brain  
Neurotransmitter release at many synapses is regulated synaptic potentials. We found a Ca 2⍣ -, Mg 2⍣ -and K ⍣dependent increase of spontaneous ACh release at both by P/Q-type Ca 2⍣ channels containing the α 1A poreforming subunit. Mutations in α 1A cause cerebral homo-and heterozygote tg NMJs. Furthermore, there was increased run-down of high-rate evoked release at disorders including familial hemiplegic migraine (FHM) and ataxia in humans. Tottering (tg) α 1A mutant mice homozygous tg NMJs.
more » ... mozygous tg NMJs. In isotonic contraction experiments this led to block of synaptic transmission at lower display ataxia and epilepsy. It is not known whether α 1A mutations induce impairment of synaptic function, which concentrations of the ACh antagonist tubocurarine than were needed in wild-type muscles. Our results suggest could underlie the symptoms of these cerebral disorders. To assess whether α 1A mutations influence neuro-that in tg motor nerve terminals there is increased influx of Ca 2⍣ under resting conditions. This study shows that transmitter release, we studied P-type Ca 2⍣ channelmediated acetylcholine (ACh) release at tg neuromuscular functional consequences of α 1A mutations causing cerebral disorders can be characterized at the NMJ. junctions (NMJs) with micro-electrode measurements of Abbreviations: ACh ϭ acetylcholine; EPP ϭ endplate potential; FHM ϭ familial hemiplegic migraine; MEPP ϭ miniature endplate potential; NMJ ϭ neuromuscular junction; PCR ϭ polymerase chain reaction; tg ϭ tottering
doi:10.1093/brain/123.3.463 pmid:10686170 fatcat:wqv3nofa5fh7josohtjmkvi4wq